{"gene":"TAF1C","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":1994,"finding":"TAF1C (TAFI110) is an integral subunit of the SL1/TIF-IB complex, binding directly and individually to TBP; when TBP is first bound by TAFI110, TFIID subunits TAFII250 and TAFII150 cannot access TBP, demonstrating mutually exclusive TBP binding between SL1 and TFIID subunits that directs promoter-selective TBP-TAF complex formation.","method":"Recombinant subunit interaction assays (complementary DNA analysis, subunit binding experiments), reconstitution of SL1 complex from purified components","journal":"Science","confidence":"High","confidence_rationale":"Tier 1 / Strong — reconstitution of complex from purified components with multiple interaction assays; foundational mechanistic study replicated by subsequent work","pmids":["7801123"],"is_preprint":false},{"year":1995,"finding":"TAFI110 (TAF1C) directly contacts the rDNA promoter as part of SL1, contributing to promoter recognition, while TAFI48 (not TAFI110) serves as the target for UBF interaction and is required for UBF-responsive transcription activation in vitro.","method":"In vitro transcription assays with purified SL1 subunits, protein-DNA contact assays","journal":"Science","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified components defining distinct functional roles of each SL1 subunit","pmids":["7491500"],"is_preprint":false},{"year":1999,"finding":"TAF1C (TAFI110) is inactivated during mitosis by cdc2/cyclin B-directed phosphorylation, leading to repression of RNA Pol I transcription; TIF-IB/SL1 activity is rapidly regained upon entry into G1 by dephosphorylation.","method":"Cell synchronization, in vitro transcription with extracts from synchronized cells, purified factors with phosphatase inhibitors","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro transcription assays with synchronized cell extracts and purified factors, replicated by later study (PMID:26023773)","pmids":["10339547"],"is_preprint":false},{"year":2000,"finding":"p53 represses RNA Pol I transcription by directly binding to SL1, with the interaction mediated primarily through contacts with TBP and TAFI110 (TAF1C); this prevents the interaction between SL1 and UBF, thereby blocking preinitiation complex assembly on the rDNA promoter.","method":"Cell-free transcription system, protein-protein interaction assays, cotransfection assays, template commitment assays, recombinant p53","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal methods including cell-free transcription reconstitution, direct binding assays, and template commitment assays in a single study","pmids":["10913176"],"is_preprint":false},{"year":2001,"finding":"hRRN3 (human RRN3) directly interacts with TAF1C (TAFI110) and TAFI63 of SL1 to recruit initiation-competent RNA Pol I (Pol Ibeta) to the rDNA promoter; blocking this connection prevents Pol I beta recruitment to the rDNA promoter.","method":"Co-immunoprecipitation, direct protein interaction assays, chromatin immunoprecipitation, in vitro transcription","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP combined with functional transcription assays and ChIP; interaction replicated by independent study (PMID:12393749)","pmids":["11250903"],"is_preprint":false},{"year":2002,"finding":"TIF-IA (mammalian RRN3 equivalent) interacts with TAF1C (TAF(I)95) of TIF-IB/SL1 through a conserved LARAK motif (amino acids 411-415); this interaction is required for association of TIF-IA with SL1 to facilitate Pol I preinitiation complex formation, and is impaired by nutrient starvation and density arrest.","method":"TIF-IA deletion mutant mapping, co-immunoprecipitation, in vitro interaction assays","journal":"EMBO reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — domain mapping with deletion mutants and multiple interaction assays; consistent with findings from PMID:11250903","pmids":["12393749"],"is_preprint":false},{"year":1997,"finding":"SV40 large T antigen directly binds to SL1 via contacts with TBP, TAFI48, and TAFI110 (TAF1C) both in vitro and in SV40-infected cells; large T antigen mutants that cannot bind SL1 also fail to stimulate Pol I transcription, indicating SL1 recruitment is required for T antigen activation of Pol I.","method":"Immunoprecipitation in vitro and from infected cells, in vitro transcription with deletion mutants, reconstituted transcription system","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — reconstituted in vitro transcription system combined with reciprocal co-IP in vivo and mutagenesis","pmids":["9203586"],"is_preprint":false},{"year":2006,"finding":"CK2 (casein kinase 2), associated specifically with the initiation-competent Pol Ibeta isoform, phosphorylates TAFI110 (TAF1C), and this phosphorylation prevents SL1 binding to rDNA, thereby abrogating SL1's ability to nucleate preinitiation complex formation.","method":"Co-immunoprecipitation, in vitro kinase assay, chromatin immunoprecipitation, in vitro transcription with CK2 inhibitor","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — direct phosphorylation assay, DNA-binding assay, in vitro transcription, and ChIP; multiple orthogonal methods in one study","pmids":["16880508"],"is_preprint":false},{"year":2008,"finding":"GSK3beta associates with the SL1 complex subunit TAF1C (TAFI110) and represses rRNA transcription; an active GSK3beta mutant abolished nucleolar BrUTP incorporation in RAS-transformed cells, and GSK3beta inhibition upregulated rRNA synthesis.","method":"Immunoprecipitation, chromatin immunoprecipitation, BrUTP nuclear run-on assay, real-time PCR, active mutant overexpression","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP showing interaction plus functional transcription assay with active mutant; single lab, multiple methods","pmids":["18490923"],"is_preprint":false},{"year":2015,"finding":"Mitotic repression of rRNA synthesis requires Cdk1/cyclin B-dependent phosphorylation of TAF1C (TAFI110) at threonine 852 (T852); upon mitotic exit, T852 is dephosphorylated by Cdc14B. Additionally, SIRT1 deacetylates another SL1 subunit TAFI68 during mitosis, destabilizing SL1 binding to the rDNA promoter; inhibiting SIRT1 alleviates mitotic repression only when T852 phosphorylation is prevented, indicating cooperative action of both modifications.","method":"Phospho-specific mutagenesis, Cdk1/cyclin B kinase assay, SIRT1 inhibition, in vitro transcription, co-immunoprecipitation","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — site-specific mutagenesis of phosphorylation site combined with kinase assays, phosphatase identification, and functional transcription analysis","pmids":["26023773"],"is_preprint":false},{"year":1999,"finding":"During F9 embryonal carcinoma differentiation into parietal endoderm, RNA Pol I transcription decreases and the abundance of TAFI95 (TAF1C) protein specifically decreases, indicating that developmental regulation of rRNA synthesis is achieved in part through reduced availability of TAF1C.","method":"Cell differentiation model, western blot for SL1 subunit levels, in vitro transcription","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — protein quantification combined with functional transcription assays in a defined differentiation model; single lab","pmids":["9933634"],"is_preprint":false},{"year":2000,"finding":"The human TAF1C gene, encoding TAFI110 (TAF1C), maps to chromosome 16q24 as a single copy gene, and is transcribed into multiple RNA species in various human tissues and cell lines, potentially producing variant SL1 isoforms.","method":"Somatic cell hybrid panel analysis, radiation hybrid panel analysis, FISH, Northern analysis","journal":"Cytogenetics and cell genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genomic localization by multiple mapping methods and transcript analysis; genomic characterization paper","pmids":["10894955"],"is_preprint":false},{"year":2025,"finding":"A homozygous missense variant in TAF1C (p.Ser589Leu) causes loss of nucleolar localization of TAF1C protein and formation of abnormal thread-like nucleoplasmic aggregates, indicating that proper subnuclear localization of TAF1C is required for its function; the mutant transcript and protein are expressed at normal levels in peripheral blood cells.","method":"Immunofluorescence microscopy, western blot, genetic analysis of patient-derived cells","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 2-3 / Weak — immunofluorescence localization in patient-derived cells with single case; novel mechanistic finding but limited to single lab/patient","pmids":["40371665"],"is_preprint":false},{"year":2020,"finding":"Homozygous TAF1C missense variants in two unrelated patients with early-onset neurological disease result in substantially reduced TAF1C mRNA and protein expression in patient-derived fibroblasts, indicating loss-of-function as the disease mechanism.","method":"RT-PCR and western blot on patient-derived fibroblasts, Sanger sequencing","journal":"Clinical genetics","confidence":"Medium","confidence_rationale":"Tier 2-3 / Weak — protein expression analysis in patient-derived cells; limited to single lab with two patients","pmids":["32779182"],"is_preprint":false},{"year":2025,"finding":"Mouse Taf1c is required for embryonic survival; homozygous mice carrying missense variants orthologous to human disease variants (Taf1cR202Q, Taf1cS428A) or an 11bp deletion allele are underrepresented at organogenesis stages, establishing an essential in vivo developmental role for Taf1c.","method":"CRISPR-Cas9 knock-in mouse models, Mendelian ratio analysis at multiple developmental stages","journal":"Developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple alleles tested in vivo with clear developmental phenotype; single lab, genetic approach","pmids":["40953792"],"is_preprint":false},{"year":2026,"finding":"TAF1C directly interacts with the H3K4 methyltransferase SETD1A and regulates H3K27ac deposition at enhancers and super-enhancers, thereby modulating lipid metabolism gene expression including ACSL4; TAF1C knockdown reduces lipid accumulation in steatotic hepatocytes in vitro and in vivo.","method":"Genome-wide CRISPR/Cas9 screen, ATAC-seq, co-immunoprecipitation, ChIP-seq, shRNA knockdown in cell and mouse models","journal":"Journal of advanced research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide screen plus Co-IP interaction and epigenomic assays; single lab, novel non-canonical function","pmids":["42031105"],"is_preprint":false}],"current_model":"TAF1C (TAFI110) is an integral subunit of the RNA Pol I-specific promoter selectivity factor SL1, where it directly contacts the rDNA promoter, binds TBP in a manner mutually exclusive with TFIID subunits, and interacts with hRRN3/TIF-IA to recruit initiation-competent Pol I; its activity is regulated by cell-cycle-dependent phosphorylation at T852 by Cdk1/cyclin B (reversed by Cdc14B at mitotic exit) and by CK2-mediated phosphorylation that prevents SL1-rDNA binding, while p53 represses Pol I transcription by binding TAFI110 to block SL1-UBF interaction; loss-of-function variants cause early-onset neurodegeneration, and a missense variant can misdirect the protein from nucleoli to nucleoplasmic aggregates."},"narrative":{"mechanistic_narrative":"TAF1C (TAFI110/TAFI95) is an integral subunit of the RNA polymerase I-specific promoter selectivity factor SL1/TIF-IB, where it controls the assembly of the rDNA preinitiation complex [PMID:7801123, PMID:7491500]. Within SL1, TAF1C binds TBP directly and in a manner mutually exclusive with the TFIID-specific TAFs, thereby committing TBP to Pol I rather than Pol II promoter recognition, and it makes direct contacts with the rDNA promoter [PMID:7801123, PMID:7491500]. TAF1C serves as the docking site that recruits initiation-competent Pol I: hRRN3/TIF-IA engages TAF1C (via a conserved LARAK motif in TIF-IA) to deliver Pol Iβ to the promoter [PMID:11250903, PMID:12393749]. This recruitment function is the principal node at which rRNA synthesis is regulated. During mitosis, Cdk1/cyclin B phosphorylates TAF1C at threonine 852 to repress transcription, a modification reversed by Cdc14B at mitotic exit and acting cooperatively with SIRT1-dependent deacetylation of the partner subunit TAFI68 [PMID:10339547, PMID:26023773]. CK2 phosphorylation of TAF1C blocks SL1 binding to rDNA [PMID:16880508], and p53 represses Pol I by binding TBP and TAF1C to prevent the SL1–UBF interaction required for preinitiation complex assembly [PMID:10913176]. SL1, through TAF1C, is also the target of growth- and oncogenic signals, being recruited by SV40 large T antigen to stimulate Pol I transcription and repressed by GSK3β association [PMID:9203586, PMID:18490923]. In humans, homozygous loss-of-function and missense TAF1C variants cause early-onset neurodegeneration, with one missense allele misdirecting the protein from nucleoli into nucleoplasmic aggregates [PMID:40371665, PMID:32779182]. A non-canonical chromatin role has also been described, in which TAF1C interacts with the H3K4 methyltransferase SETD1A and regulates enhancer H3K27ac and lipid metabolism gene expression [PMID:42031105].","teleology":[{"year":1994,"claim":"Established TAF1C as a defining SL1 subunit that imposes Pol I promoter selectivity by binding TBP mutually exclusively with TFIID TAFs, answering how a shared TBP is partitioned between polymerase systems.","evidence":"Recombinant subunit binding assays and reconstitution of SL1 from purified components","pmids":["7801123"],"confidence":"High","gaps":["No structural model of the TAF1C–TBP interface","Stoichiometry of the assembled SL1 complex not resolved here"]},{"year":1995,"claim":"Distinguished TAF1C's role in direct rDNA promoter contact from TAFI48's role as the UBF target, dividing labor among SL1 subunits during promoter recognition.","evidence":"In vitro transcription and protein–DNA contact assays with purified SL1 subunits","pmids":["7491500"],"confidence":"High","gaps":["Precise promoter sequence contacted by TAF1C not mapped","How TAF1C–DNA contacts couple to UBF responsiveness unclear"]},{"year":1997,"claim":"Showed SL1 (via TBP, TAFI48, and TAF1C) is the target through which SV40 large T antigen activates Pol I, linking SL1 recruitment to viral stimulation of rRNA synthesis.","evidence":"Co-IP in vitro and from infected cells, reconstituted transcription, and large T mutants","pmids":["9203586"],"confidence":"High","gaps":["Whether the TAF1C contact alone is sufficient for activation not isolated","Functional consequence on Pol I recruitment kinetics not measured"]},{"year":1999,"claim":"Identified mitotic Cdc2/cyclin B phosphorylation of TAF1C as the switch that represses Pol I in mitosis and is reversed in G1, establishing cell-cycle control of rRNA synthesis at the SL1 level.","evidence":"Synchronized cell extracts, in vitro transcription, phosphatase inhibitor analysis","pmids":["10339547"],"confidence":"High","gaps":["Phosphorylation site not defined in this study","Phosphatase responsible for reactivation not identified here"]},{"year":1999,"claim":"Connected developmental downregulation of rRNA synthesis to reduced TAF1C protein abundance, showing SL1 subunit availability as a regulatory parameter during differentiation.","evidence":"F9 embryonal carcinoma differentiation model, western blot, in vitro transcription","pmids":["9933634"],"confidence":"Medium","gaps":["Mechanism reducing TAF1C levels (transcriptional vs degradation) not determined","Single differentiation model"]},{"year":2000,"claim":"Defined p53 as a direct repressor of Pol I acting through binding to TBP and TAF1C to block the SL1–UBF interaction, placing tumor-suppressor control on rDNA preinitiation complex assembly.","evidence":"Cell-free transcription, protein interaction and template commitment assays, recombinant p53","pmids":["10913176"],"confidence":"High","gaps":["TAF1C residues contacted by p53 not mapped","Relative contribution of TAF1C vs TBP contacts not separated"]},{"year":2000,"claim":"Mapped the human TAF1C gene to 16q24 and detected multiple transcripts, raising the possibility of variant SL1 isoforms.","evidence":"Hybrid panel mapping, FISH, Northern analysis","pmids":["10894955"],"confidence":"Medium","gaps":["Functional distinctness of transcript variants not tested","No protein-level evidence for isoform diversity"]},{"year":2001,"claim":"Identified TAF1C (with TAFI63) as the SL1 surface that recruits hRRN3-bound initiation-competent Pol Iβ, defining the bridge between promoter recognition and polymerase delivery.","evidence":"Reciprocal Co-IP, direct interaction assays, ChIP, in vitro transcription","pmids":["11250903"],"confidence":"High","gaps":["Structure of the TAF1C–hRRN3–Pol I interface unknown","Order of assembly relative to UBF not fully resolved"]},{"year":2002,"claim":"Localized the TIF-IA contact to a conserved LARAK motif and showed the interaction is regulated by nutrient and density signals, linking growth state to SL1-dependent preinitiation.","evidence":"TIF-IA deletion mapping, Co-IP, in vitro interaction assays","pmids":["12393749"],"confidence":"High","gaps":["Reciprocal TAF1C motif binding TIF-IA not mapped","Signaling pathway transmitting nutrient status to this interaction not defined here"]},{"year":2006,"claim":"Established CK2 phosphorylation of TAF1C as a mechanism that blocks SL1–rDNA binding, adding a second kinase-controlled regulatory layer on preinitiation complex nucleation.","evidence":"Co-IP, in vitro kinase assay, ChIP, in vitro transcription with CK2 inhibitor","pmids":["16880508"],"confidence":"High","gaps":["CK2 target residues on TAF1C not identified","Interplay with Cdk1-mediated phosphorylation not addressed"]},{"year":2008,"claim":"Implicated GSK3β as a TAF1C-associated repressor of rRNA synthesis in transformed cells, extending oncogenic signaling control to SL1.","evidence":"Co-IP, ChIP, BrUTP run-on, active GSK3β mutant overexpression","pmids":["18490923"],"confidence":"Medium","gaps":["Whether GSK3β phosphorylates TAF1C directly not shown","Single-lab interaction evidence"]},{"year":2015,"claim":"Pinpointed Cdk1/cyclin B phosphorylation at TAF1C T852 (reversed by Cdc14B) and showed it cooperates with SIRT1-dependent deacetylation of TAFI68 to enforce mitotic Pol I silencing, resolving the molecular detail of cell-cycle repression.","evidence":"Phospho-site mutagenesis, Cdk1 kinase assay, SIRT1 inhibition, in vitro transcription, Co-IP","pmids":["26023773"],"confidence":"High","gaps":["Structural effect of T852 phosphorylation on SL1 not defined","Whether other mitotic kinases contribute not tested"]},{"year":2020,"claim":"Linked TAF1C to human disease, showing homozygous missense variants reduce TAF1C mRNA and protein in patient fibroblasts and cause early-onset neurological disease through loss of function.","evidence":"RT-PCR, western blot on patient fibroblasts, Sanger sequencing","pmids":["32779182"],"confidence":"Medium","gaps":["Causality not confirmed by rescue","Only two patients; mechanism linking reduced TAF1C to neurodegeneration unestablished"]},{"year":2025,"claim":"Demonstrated that proper nucleolar localization of TAF1C is required for function, with a p.Ser589Leu variant mislocalizing the protein to nucleoplasmic aggregates despite normal expression levels.","evidence":"Immunofluorescence and western blot in patient-derived cells","pmids":["40371665"],"confidence":"Medium","gaps":["Single patient","Direct link between aggregation and Pol I transcription defect not measured"]},{"year":2025,"claim":"Established an essential in vivo developmental role for Taf1c, with disease-orthologous and deletion alleles causing embryonic lethality at organogenesis in mice.","evidence":"CRISPR knock-in mouse models, Mendelian ratio analysis across developmental stages","pmids":["40953792"],"confidence":"Medium","gaps":["Tissue-specific requirement not dissected","Molecular cause of lethality (rRNA synthesis failure) not directly demonstrated"]},{"year":2026,"claim":"Revealed a non-canonical chromatin function in which TAF1C interacts with SETD1A and regulates enhancer H3K27ac and lipid metabolism genes, expanding TAF1C beyond Pol I transcription.","evidence":"Genome-wide CRISPR screen, ATAC-seq, Co-IP, ChIP-seq, shRNA in cell and mouse models","pmids":["42031105"],"confidence":"Medium","gaps":["Whether this function is independent of SL1/Pol I role unclear","Single lab; mechanism of TAF1C recruitment to enhancers not defined"]},{"year":null,"claim":"How loss of TAF1C-dependent Pol I activity produces selective neurodegeneration, and how its canonical rDNA role relates to the newly described enhancer/SETD1A function, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mechanistic link between reduced rRNA synthesis and neuronal vulnerability","Relationship between nucleolar and chromatin functions unestablished","No structural model of the assembled SL1 complex"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[1]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,4]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[12]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,4]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,4]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,9]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[15]}],"complexes":["SL1/TIF-IB"],"partners":["TBP","RRN3","TP53","CSNK2A1","GSK3B","SETD1A","TAF1A","TAF1B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15572","full_name":"TATA box-binding protein-associated factor RNA polymerase I subunit C","aliases":["RNA polymerase I-specific TBP-associated factor 110 kDa","TAFI110","TATA box-binding protein-associated factor 1C","TBP-associated factor 1C","Transcription initiation factor SL1/TIF-IB subunit C"],"length_aa":869,"mass_kda":95.2,"function":"Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits. Recruits RNA polymerase I to the rRNA gene promoter via interaction with RRN3","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q15572/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/TAF1C","classification":"Common Essential","n_dependent_lines":1177,"n_total_lines":1208,"dependency_fraction":0.9743377483443708},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TAF1C","total_profiled":1310},"omim":[{"mim_id":"612823","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 1D; TAF1D","url":"https://www.omim.org/entry/612823"},{"mim_id":"605004","title":"GLYCOGEN SYNTHASE KINASE 3-BETA; GSK3B","url":"https://www.omim.org/entry/605004"},{"mim_id":"604905","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 1C; TAF1C","url":"https://www.omim.org/entry/604905"},{"mim_id":"604904","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 1B; TAF1B","url":"https://www.omim.org/entry/604904"},{"mim_id":"604903","title":"TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR 1A; TAF1A","url":"https://www.omim.org/entry/604903"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli fibrillar center","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAF1C"},"hgnc":{"alias_symbol":["TAFI110","TAFI95","SL1","MGC:39976"],"prev_symbol":[]},"alphafold":{"accession":"Q15572","domains":[{"cath_id":"-","chopping":"83-133_147-155_166-206","consensus_level":"high","plddt":68.5773,"start":83,"end":206}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15572","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15572-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15572-F1-predicted_aligned_error_v6.png","plddt_mean":64.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAF1C","jax_strain_url":"https://www.jax.org/strain/search?query=TAF1C"},"sequence":{"accession":"Q15572","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15572.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15572/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15572"}},"corpus_meta":[{"pmid":"10913176","id":"PMC_10913176","title":"Repression of RNA polymerase I transcription by the tumor suppressor p53.","date":"2000","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10913176","citation_count":229,"is_preprint":false},{"pmid":"24436420","id":"PMC_24436420","title":"Changes in rRNA transcription influence proliferation and cell fate within a stem cell lineage.","date":"2014","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/24436420","citation_count":161,"is_preprint":false},{"pmid":"11250903","id":"PMC_11250903","title":"hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA gene promoters.","date":"2001","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/11250903","citation_count":155,"is_preprint":false},{"pmid":"10339547","id":"PMC_10339547","title":"Cell cycle-dependent regulation of RNA polymerase I transcription: the nucleolar transcription factor UBF is inactive in mitosis and early G1.","date":"1999","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/10339547","citation_count":143,"is_preprint":false},{"pmid":"7801123","id":"PMC_7801123","title":"Reconstitution of transcription factor SL1: exclusive binding of TBP by SL1 or TFIID subunits.","date":"1994","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/7801123","citation_count":134,"is_preprint":false},{"pmid":"25969726","id":"PMC_25969726","title":"Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.","date":"2015","source":"Molecular autism","url":"https://pubmed.ncbi.nlm.nih.gov/25969726","citation_count":103,"is_preprint":false},{"pmid":"7491500","id":"PMC_7491500","title":"Coactivator and promoter-selective properties of RNA polymerase I TAFs.","date":"1995","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/7491500","citation_count":86,"is_preprint":false},{"pmid":"22403788","id":"PMC_22403788","title":"Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy.","date":"2012","source":"American journal of physiology. 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directly and individually to TBP; when TBP is first bound by TAFI110, TFIID subunits TAFII250 and TAFII150 cannot access TBP, demonstrating mutually exclusive TBP binding between SL1 and TFIID subunits that directs promoter-selective TBP-TAF complex formation.\",\n      \"method\": \"Recombinant subunit interaction assays (complementary DNA analysis, subunit binding experiments), reconstitution of SL1 complex from purified components\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — reconstitution of complex from purified components with multiple interaction assays; foundational mechanistic study replicated by subsequent work\",\n      \"pmids\": [\"7801123\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"TAFI110 (TAF1C) directly contacts the rDNA promoter as part of SL1, contributing to promoter recognition, while TAFI48 (not TAFI110) serves as the target for UBF interaction and is required for UBF-responsive transcription activation in vitro.\",\n      \"method\": \"In vitro transcription assays with purified SL1 subunits, protein-DNA contact assays\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified components defining distinct functional roles of each SL1 subunit\",\n      \"pmids\": [\"7491500\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"TAF1C (TAFI110) is inactivated during mitosis by cdc2/cyclin B-directed phosphorylation, leading to repression of RNA Pol I transcription; TIF-IB/SL1 activity is rapidly regained upon entry into G1 by dephosphorylation.\",\n      \"method\": \"Cell synchronization, in vitro transcription with extracts from synchronized cells, purified factors with phosphatase inhibitors\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro transcription assays with synchronized cell extracts and purified factors, replicated by later study (PMID:26023773)\",\n      \"pmids\": [\"10339547\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"p53 represses RNA Pol I transcription by directly binding to SL1, with the interaction mediated primarily through contacts with TBP and TAFI110 (TAF1C); this prevents the interaction between SL1 and UBF, thereby blocking preinitiation complex assembly on the rDNA promoter.\",\n      \"method\": \"Cell-free transcription system, protein-protein interaction assays, cotransfection assays, template commitment assays, recombinant p53\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal methods including cell-free transcription reconstitution, direct binding assays, and template commitment assays in a single study\",\n      \"pmids\": [\"10913176\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"hRRN3 (human RRN3) directly interacts with TAF1C (TAFI110) and TAFI63 of SL1 to recruit initiation-competent RNA Pol I (Pol Ibeta) to the rDNA promoter; blocking this connection prevents Pol I beta recruitment to the rDNA promoter.\",\n      \"method\": \"Co-immunoprecipitation, direct protein interaction assays, chromatin immunoprecipitation, in vitro transcription\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP combined with functional transcription assays and ChIP; interaction replicated by independent study (PMID:12393749)\",\n      \"pmids\": [\"11250903\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"TIF-IA (mammalian RRN3 equivalent) interacts with TAF1C (TAF(I)95) of TIF-IB/SL1 through a conserved LARAK motif (amino acids 411-415); this interaction is required for association of TIF-IA with SL1 to facilitate Pol I preinitiation complex formation, and is impaired by nutrient starvation and density arrest.\",\n      \"method\": \"TIF-IA deletion mutant mapping, co-immunoprecipitation, in vitro interaction assays\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — domain mapping with deletion mutants and multiple interaction assays; consistent with findings from PMID:11250903\",\n      \"pmids\": [\"12393749\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"SV40 large T antigen directly binds to SL1 via contacts with TBP, TAFI48, and TAFI110 (TAF1C) both in vitro and in SV40-infected cells; large T antigen mutants that cannot bind SL1 also fail to stimulate Pol I transcription, indicating SL1 recruitment is required for T antigen activation of Pol I.\",\n      \"method\": \"Immunoprecipitation in vitro and from infected cells, in vitro transcription with deletion mutants, reconstituted transcription system\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — reconstituted in vitro transcription system combined with reciprocal co-IP in vivo and mutagenesis\",\n      \"pmids\": [\"9203586\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CK2 (casein kinase 2), associated specifically with the initiation-competent Pol Ibeta isoform, phosphorylates TAFI110 (TAF1C), and this phosphorylation prevents SL1 binding to rDNA, thereby abrogating SL1's ability to nucleate preinitiation complex formation.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, chromatin immunoprecipitation, in vitro transcription with CK2 inhibitor\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — direct phosphorylation assay, DNA-binding assay, in vitro transcription, and ChIP; multiple orthogonal methods in one study\",\n      \"pmids\": [\"16880508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"GSK3beta associates with the SL1 complex subunit TAF1C (TAFI110) and represses rRNA transcription; an active GSK3beta mutant abolished nucleolar BrUTP incorporation in RAS-transformed cells, and GSK3beta inhibition upregulated rRNA synthesis.\",\n      \"method\": \"Immunoprecipitation, chromatin immunoprecipitation, BrUTP nuclear run-on assay, real-time PCR, active mutant overexpression\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP showing interaction plus functional transcription assay with active mutant; single lab, multiple methods\",\n      \"pmids\": [\"18490923\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Mitotic repression of rRNA synthesis requires Cdk1/cyclin B-dependent phosphorylation of TAF1C (TAFI110) at threonine 852 (T852); upon mitotic exit, T852 is dephosphorylated by Cdc14B. Additionally, SIRT1 deacetylates another SL1 subunit TAFI68 during mitosis, destabilizing SL1 binding to the rDNA promoter; inhibiting SIRT1 alleviates mitotic repression only when T852 phosphorylation is prevented, indicating cooperative action of both modifications.\",\n      \"method\": \"Phospho-specific mutagenesis, Cdk1/cyclin B kinase assay, SIRT1 inhibition, in vitro transcription, co-immunoprecipitation\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — site-specific mutagenesis of phosphorylation site combined with kinase assays, phosphatase identification, and functional transcription analysis\",\n      \"pmids\": [\"26023773\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"During F9 embryonal carcinoma differentiation into parietal endoderm, RNA Pol I transcription decreases and the abundance of TAFI95 (TAF1C) protein specifically decreases, indicating that developmental regulation of rRNA synthesis is achieved in part through reduced availability of TAF1C.\",\n      \"method\": \"Cell differentiation model, western blot for SL1 subunit levels, in vitro transcription\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — protein quantification combined with functional transcription assays in a defined differentiation model; single lab\",\n      \"pmids\": [\"9933634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The human TAF1C gene, encoding TAFI110 (TAF1C), maps to chromosome 16q24 as a single copy gene, and is transcribed into multiple RNA species in various human tissues and cell lines, potentially producing variant SL1 isoforms.\",\n      \"method\": \"Somatic cell hybrid panel analysis, radiation hybrid panel analysis, FISH, Northern analysis\",\n      \"journal\": \"Cytogenetics and cell genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genomic localization by multiple mapping methods and transcript analysis; genomic characterization paper\",\n      \"pmids\": [\"10894955\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A homozygous missense variant in TAF1C (p.Ser589Leu) causes loss of nucleolar localization of TAF1C protein and formation of abnormal thread-like nucleoplasmic aggregates, indicating that proper subnuclear localization of TAF1C is required for its function; the mutant transcript and protein are expressed at normal levels in peripheral blood cells.\",\n      \"method\": \"Immunofluorescence microscopy, western blot, genetic analysis of patient-derived cells\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Weak — immunofluorescence localization in patient-derived cells with single case; novel mechanistic finding but limited to single lab/patient\",\n      \"pmids\": [\"40371665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Homozygous TAF1C missense variants in two unrelated patients with early-onset neurological disease result in substantially reduced TAF1C mRNA and protein expression in patient-derived fibroblasts, indicating loss-of-function as the disease mechanism.\",\n      \"method\": \"RT-PCR and western blot on patient-derived fibroblasts, Sanger sequencing\",\n      \"journal\": \"Clinical genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Weak — protein expression analysis in patient-derived cells; limited to single lab with two patients\",\n      \"pmids\": [\"32779182\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Mouse Taf1c is required for embryonic survival; homozygous mice carrying missense variants orthologous to human disease variants (Taf1cR202Q, Taf1cS428A) or an 11bp deletion allele are underrepresented at organogenesis stages, establishing an essential in vivo developmental role for Taf1c.\",\n      \"method\": \"CRISPR-Cas9 knock-in mouse models, Mendelian ratio analysis at multiple developmental stages\",\n      \"journal\": \"Developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple alleles tested in vivo with clear developmental phenotype; single lab, genetic approach\",\n      \"pmids\": [\"40953792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"TAF1C directly interacts with the H3K4 methyltransferase SETD1A and regulates H3K27ac deposition at enhancers and super-enhancers, thereby modulating lipid metabolism gene expression including ACSL4; TAF1C knockdown reduces lipid accumulation in steatotic hepatocytes in vitro and in vivo.\",\n      \"method\": \"Genome-wide CRISPR/Cas9 screen, ATAC-seq, co-immunoprecipitation, ChIP-seq, shRNA knockdown in cell and mouse models\",\n      \"journal\": \"Journal of advanced research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide screen plus Co-IP interaction and epigenomic assays; single lab, novel non-canonical function\",\n      \"pmids\": [\"42031105\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAF1C (TAFI110) is an integral subunit of the RNA Pol I-specific promoter selectivity factor SL1, where it directly contacts the rDNA promoter, binds TBP in a manner mutually exclusive with TFIID subunits, and interacts with hRRN3/TIF-IA to recruit initiation-competent Pol I; its activity is regulated by cell-cycle-dependent phosphorylation at T852 by Cdk1/cyclin B (reversed by Cdc14B at mitotic exit) and by CK2-mediated phosphorylation that prevents SL1-rDNA binding, while p53 represses Pol I transcription by binding TAFI110 to block SL1-UBF interaction; loss-of-function variants cause early-onset neurodegeneration, and a missense variant can misdirect the protein from nucleoli to nucleoplasmic aggregates.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TAF1C (TAFI110/TAFI95) is an integral subunit of the RNA polymerase I-specific promoter selectivity factor SL1/TIF-IB, where it controls the assembly of the rDNA preinitiation complex [#0, #1]. Within SL1, TAF1C binds TBP directly and in a manner mutually exclusive with the TFIID-specific TAFs, thereby committing TBP to Pol I rather than Pol II promoter recognition, and it makes direct contacts with the rDNA promoter [#0, #1]. TAF1C serves as the docking site that recruits initiation-competent Pol I: hRRN3/TIF-IA engages TAF1C (via a conserved LARAK motif in TIF-IA) to deliver Pol Iβ to the promoter [#4, #5]. This recruitment function is the principal node at which rRNA synthesis is regulated. During mitosis, Cdk1/cyclin B phosphorylates TAF1C at threonine 852 to repress transcription, a modification reversed by Cdc14B at mitotic exit and acting cooperatively with SIRT1-dependent deacetylation of the partner subunit TAFI68 [#2, #9]. CK2 phosphorylation of TAF1C blocks SL1 binding to rDNA [#7], and p53 represses Pol I by binding TBP and TAF1C to prevent the SL1–UBF interaction required for preinitiation complex assembly [#3]. SL1, through TAF1C, is also the target of growth- and oncogenic signals, being recruited by SV40 large T antigen to stimulate Pol I transcription and repressed by GSK3β association [#6, #8]. In humans, homozygous loss-of-function and missense TAF1C variants cause early-onset neurodegeneration, with one missense allele misdirecting the protein from nucleoli into nucleoplasmic aggregates [#12, #13]. A non-canonical chromatin role has also been described, in which TAF1C interacts with the H3K4 methyltransferase SETD1A and regulates enhancer H3K27ac and lipid metabolism gene expression [#15].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Established TAF1C as a defining SL1 subunit that imposes Pol I promoter selectivity by binding TBP mutually exclusively with TFIID TAFs, answering how a shared TBP is partitioned between polymerase systems.\",\n      \"evidence\": \"Recombinant subunit binding assays and reconstitution of SL1 from purified components\",\n      \"pmids\": [\"7801123\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of the TAF1C–TBP interface\", \"Stoichiometry of the assembled SL1 complex not resolved here\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Distinguished TAF1C's role in direct rDNA promoter contact from TAFI48's role as the UBF target, dividing labor among SL1 subunits during promoter recognition.\",\n      \"evidence\": \"In vitro transcription and protein–DNA contact assays with purified SL1 subunits\",\n      \"pmids\": [\"7491500\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise promoter sequence contacted by TAF1C not mapped\", \"How TAF1C–DNA contacts couple to UBF responsiveness unclear\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Showed SL1 (via TBP, TAFI48, and TAF1C) is the target through which SV40 large T antigen activates Pol I, linking SL1 recruitment to viral stimulation of rRNA synthesis.\",\n      \"evidence\": \"Co-IP in vitro and from infected cells, reconstituted transcription, and large T mutants\",\n      \"pmids\": [\"9203586\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether the TAF1C contact alone is sufficient for activation not isolated\", \"Functional consequence on Pol I recruitment kinetics not measured\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identified mitotic Cdc2/cyclin B phosphorylation of TAF1C as the switch that represses Pol I in mitosis and is reversed in G1, establishing cell-cycle control of rRNA synthesis at the SL1 level.\",\n      \"evidence\": \"Synchronized cell extracts, in vitro transcription, phosphatase inhibitor analysis\",\n      \"pmids\": [\"10339547\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phosphorylation site not defined in this study\", \"Phosphatase responsible for reactivation not identified here\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Connected developmental downregulation of rRNA synthesis to reduced TAF1C protein abundance, showing SL1 subunit availability as a regulatory parameter during differentiation.\",\n      \"evidence\": \"F9 embryonal carcinoma differentiation model, western blot, in vitro transcription\",\n      \"pmids\": [\"9933634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism reducing TAF1C levels (transcriptional vs degradation) not determined\", \"Single differentiation model\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Defined p53 as a direct repressor of Pol I acting through binding to TBP and TAF1C to block the SL1–UBF interaction, placing tumor-suppressor control on rDNA preinitiation complex assembly.\",\n      \"evidence\": \"Cell-free transcription, protein interaction and template commitment assays, recombinant p53\",\n      \"pmids\": [\"10913176\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"TAF1C residues contacted by p53 not mapped\", \"Relative contribution of TAF1C vs TBP contacts not separated\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Mapped the human TAF1C gene to 16q24 and detected multiple transcripts, raising the possibility of variant SL1 isoforms.\",\n      \"evidence\": \"Hybrid panel mapping, FISH, Northern analysis\",\n      \"pmids\": [\"10894955\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional distinctness of transcript variants not tested\", \"No protein-level evidence for isoform diversity\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Identified TAF1C (with TAFI63) as the SL1 surface that recruits hRRN3-bound initiation-competent Pol Iβ, defining the bridge between promoter recognition and polymerase delivery.\",\n      \"evidence\": \"Reciprocal Co-IP, direct interaction assays, ChIP, in vitro transcription\",\n      \"pmids\": [\"11250903\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure of the TAF1C–hRRN3–Pol I interface unknown\", \"Order of assembly relative to UBF not fully resolved\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Localized the TIF-IA contact to a conserved LARAK motif and showed the interaction is regulated by nutrient and density signals, linking growth state to SL1-dependent preinitiation.\",\n      \"evidence\": \"TIF-IA deletion mapping, Co-IP, in vitro interaction assays\",\n      \"pmids\": [\"12393749\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Reciprocal TAF1C motif binding TIF-IA not mapped\", \"Signaling pathway transmitting nutrient status to this interaction not defined here\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Established CK2 phosphorylation of TAF1C as a mechanism that blocks SL1–rDNA binding, adding a second kinase-controlled regulatory layer on preinitiation complex nucleation.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, ChIP, in vitro transcription with CK2 inhibitor\",\n      \"pmids\": [\"16880508\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"CK2 target residues on TAF1C not identified\", \"Interplay with Cdk1-mediated phosphorylation not addressed\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Implicated GSK3β as a TAF1C-associated repressor of rRNA synthesis in transformed cells, extending oncogenic signaling control to SL1.\",\n      \"evidence\": \"Co-IP, ChIP, BrUTP run-on, active GSK3β mutant overexpression\",\n      \"pmids\": [\"18490923\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether GSK3β phosphorylates TAF1C directly not shown\", \"Single-lab interaction evidence\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Pinpointed Cdk1/cyclin B phosphorylation at TAF1C T852 (reversed by Cdc14B) and showed it cooperates with SIRT1-dependent deacetylation of TAFI68 to enforce mitotic Pol I silencing, resolving the molecular detail of cell-cycle repression.\",\n      \"evidence\": \"Phospho-site mutagenesis, Cdk1 kinase assay, SIRT1 inhibition, in vitro transcription, Co-IP\",\n      \"pmids\": [\"26023773\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural effect of T852 phosphorylation on SL1 not defined\", \"Whether other mitotic kinases contribute not tested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked TAF1C to human disease, showing homozygous missense variants reduce TAF1C mRNA and protein in patient fibroblasts and cause early-onset neurological disease through loss of function.\",\n      \"evidence\": \"RT-PCR, western blot on patient fibroblasts, Sanger sequencing\",\n      \"pmids\": [\"32779182\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causality not confirmed by rescue\", \"Only two patients; mechanism linking reduced TAF1C to neurodegeneration unestablished\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated that proper nucleolar localization of TAF1C is required for function, with a p.Ser589Leu variant mislocalizing the protein to nucleoplasmic aggregates despite normal expression levels.\",\n      \"evidence\": \"Immunofluorescence and western blot in patient-derived cells\",\n      \"pmids\": [\"40371665\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single patient\", \"Direct link between aggregation and Pol I transcription defect not measured\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established an essential in vivo developmental role for Taf1c, with disease-orthologous and deletion alleles causing embryonic lethality at organogenesis in mice.\",\n      \"evidence\": \"CRISPR knock-in mouse models, Mendelian ratio analysis across developmental stages\",\n      \"pmids\": [\"40953792\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Tissue-specific requirement not dissected\", \"Molecular cause of lethality (rRNA synthesis failure) not directly demonstrated\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Revealed a non-canonical chromatin function in which TAF1C interacts with SETD1A and regulates enhancer H3K27ac and lipid metabolism genes, expanding TAF1C beyond Pol I transcription.\",\n      \"evidence\": \"Genome-wide CRISPR screen, ATAC-seq, Co-IP, ChIP-seq, shRNA in cell and mouse models\",\n      \"pmids\": [\"42031105\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this function is independent of SL1/Pol I role unclear\", \"Single lab; mechanism of TAF1C recruitment to enhancers not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How loss of TAF1C-dependent Pol I activity produces selective neurodegeneration, and how its canonical rDNA role relates to the newly described enhancer/SETD1A function, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mechanistic link between reduced rRNA synthesis and neuronal vulnerability\", \"Relationship between nucleolar and chromatin functions unestablished\", \"No structural model of the assembled SL1 complex\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 9]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [15]}\n    ],\n    \"complexes\": [\"SL1/TIF-IB\"],\n    \"partners\": [\"TBP\", \"RRN3\", \"TP53\", \"CSNK2A1\", \"GSK3B\", \"SETD1A\", \"TAF1A\", \"TAF1B\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}