Affinage

PAF1

Peroxisome biogenesis factor 2 · UniProt P28328

Length
305 aa
Mass
34.8 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PAF1 is the core subunit of the conserved RNA polymerase II-associated PAF1 complex (PAF1C; Paf1, Ctr9, Cdc73/parafibromin, Rtf1, Leo1), which travels with Pol II across promoters and coding regions of active genes and couples transcription elongation to chromatin modification and RNA 3'-end processing (PMID:11927560, PMID:11884586, PMID:15149594, PMID:15923622). Structurally, PAF1 nucleates assembly through a tightly intertwined Ctr9/Paf1 heterodimer and a Paf1/Leo1 heterodimer that together bind histone H3, the octamer, and the nucleosome; loss of the Ctr9-Paf1 interface abolishes complex assembly and histone H3 methylation in vivo (PMID:24038468, PMID:30228257). PAF1C directs co-transcriptional histone marks—H3K4 methylation via MLL1/Set1 and Rtf1-stimulated Rad6-dependent H2B K123 ubiquitylation—and modulates nucleosome dynamics and recruitment of Spt6/FACT during active transcription (PMID:16354696, PMID:22046413, PMID:30228257, PMID:37216505). In metazoans PAF1 is a central regulator of Pol II promoter-proximal pausing, restraining release into gene bodies by limiting super elongation complex (SEC) access and by recruiting the Integrator-PP2A (INTAC) complex to skew the balance against P-TEFb-driven SPT5 phosphorylation (PMID:26279188, PMID:35363521); this pausing control extends to enhancers, where PAF1 restrains hyperactivation that would otherwise release paused Pol II at target promoters (PMID:28860207). PAF1C also promotes 3'-end processing and termination of mRNAs, snoRNAs, and pervasive transcripts (eRNAs/PROMPTs) through interactions with cleavage/polyadenylation factor Cft1 and Integrator (PMID:18469135, PMID:35294889, PMID:23109428), and by ensuring efficient termination and nascent-transcript release it prevents RNAi/piRNA-directed heterochromatin spreading (PMID:25807481, PMID:26518661, PMID:28844648). Beyond canonical PAF1C functions, PAF1 maintains embryonic stem cell self-renewal through physical interaction with Oct3/4 (PMID:19821493) and, independently of PAF1C, forms a PHF5A-DDX3 sub-complex that binds the Nanog promoter to drive cancer stem cell programs (PMID:32781084).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2002 High

    Established PAF1 as the defining subunit of a Pol II-associated complex distinct from Srb-mediator, answering whether PAF1 acts on transcription and through what assembly.

    Evidence Affinity/TAP purification with mass spectrometry, reciprocal Co-IP, and genetic epistasis with elongation factors in yeast

    PMID:11884586 PMID:11927560

    Open questions at the time
    • Direct mechanistic step in elongation not yet defined
    • Functional consequence on specific histone marks not yet established
  2. 2004 High

    Showed PAF1C physically travels with Pol II on active genes and influences CTD Ser2 phosphorylation and poly(A) tail length, linking the complex to both elongation and RNA fate.

    Evidence ChIP localization, poly(A) tail analysis, and fractionation across subunit-deletion backgrounds in yeast

    PMID:15149594

    Open questions at the time
    • Whether Ser2P change is direct or indirect unresolved
    • Mechanism coupling Paf1C to poly(A) machinery not defined
  3. 2005 High

    Extended PAF1C to humans and tied it to the tumor suppressor parafibromin, connecting the complex to a clinically mutated subunit.

    Evidence Reciprocal Co-IP, RNAi, domain-deletion mapping, and CTD phospho-form association in human cells

    PMID:15923622

    Open questions at the time
    • Disease-causing mechanism of parafibromin loss not established here
    • Direct enzymatic activity not addressed
  4. 2006 High

    Defined a metazoan role in chromatin modulation during active transcription, showing PAF1 is required for H3K4me3 and Spt6/FACT recruitment at induced genes.

    Evidence RNAi depletion with ChIP, polytene immunofluorescence, and RNA induction assays in Drosophila

    PMID:16354696

    Open questions at the time
    • Direct vs. indirect effect on H3K4me3 unresolved
    • Whether PAF1 recruits the methyltransferase directly not shown
  5. 2008 High

    Mechanistically linked PAF1C to 3'-end processing via a direct Cft1 interaction, explaining polyadenylation read-through phenotypes.

    Evidence Co-IP detecting Cft1-Paf1C interaction and read-through/CTD phospho assays across subunit deletions in yeast

    PMID:18469135

    Open questions at the time
    • Why interaction is masked on Pol II-bound Paf1C not fully explained
    • Generality across genes not tested genome-wide here
  6. 2009 Medium

    Connected PAF1 to pluripotency, showing it interacts with Oct3/4 and sustains ESC self-renewal.

    Evidence Co-IP, knockdown/knockout ESCs, flow cytometry, and pluripotency gene expression analysis

    PMID:19821493

    Open questions at the time
    • Whether the Oct3/4 effect requires PAF1C integrity not resolved
    • Single lab; direct chromatin targets at pluripotency genes not mapped
  7. 2011 Medium

    Linked PAF1 to chromatin remodeling output by showing it supports MLL1-dependent H3K4 methylation and CHD1 nuclear localization in cancer cells.

    Evidence siRNA knockdown, Co-IP, confocal co-localization, MNase digestion, and rescue in pancreatic cancer cells

    PMID:22046413

    Open questions at the time
    • Directness of PAF1-MLL1 regulation not established
    • Single lab and cell-type specific
  8. 2012 Medium

    Generalized PAF1C 3'-processing function to snoRNAs, showing locus-specific dependence on distinct PAF1-controlled histone marks acting with Nrd1/Nab3.

    Evidence Transcriptome-wide tiling arrays, ChIP, and epistasis with deletion strains in yeast

    PMID:23109428

    Open questions at the time
    • Basis of locus-specific mark requirement unexplained
    • Some Rad6 effects uncoupled from H2Bub mechanistically unclear
  9. 2013 High

    Provided structural basis for assembly and nucleosome engagement, defining the PAF1/LEO1 heterodimer and CTR9 as scaffold.

    Evidence X-ray crystallography of human PAF1/LEO1 plus in vitro histone/nucleosome binding assays

    PMID:24038468

    Open questions at the time
    • Functional consequence of nucleosome binding in vivo not shown
    • Full-complex architecture not resolved here
  10. 2014 Medium

    Placed PAF1 in an H2BK34ub-dependent positive feedback loop stabilizing chromatin factors and pTEFb during early elongation.

    Evidence Co-IP binary-interaction mapping, ChIP-seq, siRNA, and Pol II processivity assays

    PMID:24837678

    Open questions at the time
    • Direct vs. cooperative recruitment not fully separated
    • Single lab
  11. 2015 High

    Established PAF1 as a conserved regulator of promoter-proximal pausing that restrains SEC-driven pause release, distinguishing pausing control from elongation per se.

    Evidence siRNA depletion with GRO-seq, ChIP-seq, and RNA-seq in human cells

    PMID:26279188

    Open questions at the time
    • How PAF1 limits SEC recruitment mechanistically not fully defined here
    • Locus determinants of pausing sensitivity unclear
  12. 2015 High

    Defined a chromatin-protective role in which PAF1C-driven termination and transcript release prevent RNAi-directed and spreading heterochromatin.

    Evidence Genetic screens, heterochromatin reporters, RNA-seq, ChIP/ChIP-exo, and histone turnover assays in fission yeast

    PMID:25807481 PMID:26518661

    Open questions at the time
    • Molecular step coupling release to RNAi suppression not fully resolved
    • Relevance to metazoan heterochromatin not tested here
  13. 2017 High

    Distinguished elongation from RNA-fate roles by showing Paf1 occupancy is dynamic and promoter-tuned, coupling high occupancy to nuclear export.

    Evidence NET-seq at nucleotide resolution with yeast genetics across mutant strains

    PMID:28190769

    Open questions at the time
    • Mechanism linking Paf1 level to export factor loading not defined
    • How promoters set Paf1 occupancy unknown
  14. 2017 High

    Extended PAF1 pausing control to enhancers, showing it restrains enhancer hyperactivation that drives pause release at cognate promoters.

    Evidence ChIP-seq, CRISPR enhancer knockout, and GRO-seq in human cells

    PMID:28860207

    Open questions at the time
    • How PAF1 represses enhancer activity mechanistically not defined
    • Selectivity for enhancer subsets unexplained
  15. 2017 Medium

    Demonstrated conservation of PAF1's antagonism of small-RNA-directed silencing, here against PIWI/piRNA pathways downstream of initial silencing.

    Evidence RNAi with piRNA-targeted reporters and transposable-element expression in Drosophila OSS cells

    PMID:28844648

    Open questions at the time
    • Single model and lab
    • Precise step downstream of PIWI not pinpointed
  16. 2018 Medium

    Revealed a PAF1C-independent oncogenic function: a PAF1-PHF5A-DDX3 sub-complex binds the Nanog promoter to sustain cancer stem cells.

    Evidence Co-IP/MS, ChIP-seq, CRISPR KO, shRNA, orthotopic tumor models, and DDX3 inhibitor in pancreatic CSCs

    PMID:32781084

    Open questions at the time
    • Structural basis of the sub-complex unknown
    • Single lab; generality across tumor types untested
  17. 2018 Medium

    Implicated PAF1C in selectively transcribing toxic GGGGCC repeat expansions, connecting it to C9orf72 FTD/ALS pathology.

    Evidence Unbiased Drosophila genetic screen, RNA/dipeptide quantification, and LEO1 ChIP in human C9+ cells

    PMID:31110321

    Open questions at the time
    • Why long repeats are selectively favored not mechanistically resolved
    • Single lab
  18. 2019 Medium

    Uncovered a repressive PAF1C function: promoter-bound Paf1C represses ATG32 to suppress mitophagy until glucose starvation triggers its dissociation.

    Evidence ChIP of promoter binding, gene deletions, RT-qPCR, mitophagy assays with mammalian validation

    PMID:31525119

    Open questions at the time
    • Signal coupling starvation to Paf1C dissociation unknown
    • Mechanism of repression at the promoter undefined
  19. 2021 Medium

    Defined an antiviral role and a viral evasion mechanism, with Dengue NS5 binding PAF1C to block its recruitment to STAT2-independent immune genes.

    Evidence Co-IP with NS5 domain mapping, PAF1 CRISPR KO, RNA-seq, and viral titer assays

    PMID:34797876

    Open questions at the time
    • How NS5 displaces PAF1C from chromatin not resolved
    • Breadth of immune gene set incompletely mapped
  20. 2022 High

    Mechanistically resolved the pausing function via acute degradation, showing PAF1 recruits INTAC to balance against P-TEFb and limits SPT5 hyperphosphorylation.

    Evidence Rapid degron, ChIP-seq, GRO-seq, mass spectrometry, and phospho-proteomics in human cells

    PMID:35363521

    Open questions at the time
    • How PAF1 physically delivers INTAC to paused Pol II not fully defined
    • Relative contribution of histone-mark loss vs. direct effects unresolved
  21. 2022 Medium

    Showed PAF1C promotes Integrator-dependent 3' cleavage/termination of pervasive transcripts and dissociates from Integrator upon processive elongation.

    Evidence PAF1C depletion/degradation with PRO-seq, ChIP-seq, and Co-IP in human cells

    PMID:35294889

    Open questions at the time
    • Switch controlling Integrator handoff at elongation entry undefined
    • Single lab
  22. 2023 High

    Resolved the molecular basis of PAF1C-driven H2B ubiquitylation, mapping a direct Rtf1-HMD/Rad6 contact that stimulates H2BK123ub.

    Evidence Cross-linking/MS, in vitro ubiquitylation, separation-of-function RAD6 alleles, and RNA-seq in yeast

    PMID:37216505

    Open questions at the time
    • How H2Bub feeds into downstream elongation/termination not fully traced
    • Structural model of the Rtf1-Rad6-nucleosome complex absent

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PAF1 physically integrates its dual roles—delivering INTAC/3'-processing factors versus restraining SEC—into a single dynamic occupancy program across the transcription cycle, and how PAF1C-independent sub-complexes are partitioned mechanistically.
  • No unified structural model of PAF1 engaging paused vs. elongating Pol II
  • Determinants partitioning PAF1 between PAF1C and PHF5A-DDX3 sub-complexes unknown
  • How environmental/promoter signals set Paf1 occupancy is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140110 transcription regulator activity 4 GO:0005198 structural molecule activity 2 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1266738 Developmental Biology 2
Partners
CDC73CFT1CTR9LEO1OCT4PHF5ARAD6RTF1
Complex memberships
PAF1 complex (PAF1C)PAF1-PHF5A-DDX3 sub-complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PAF1 (Paf1) and Leo1 are components of the RNA polymerase II-associated Paf1 complex, which physically interacts with transcription elongation factors Spt4-Spt5 and Spt16-Pob3 (yeast FACT). Genetic and physical interactions were demonstrated, and loss of Paf1 complex function causes 6-azauracil sensitivity and diminished PUR5 induction, consistent with impaired transcription elongation. Affinity purification, mass spectrometry, Co-IP, genetic suppressor screen, 6-azauracil sensitivity assay The EMBO journal High 11927560
2002 Ctr9, Rtf1, and Leo1 are components of the yeast Paf1 complex associated with Pol II but not Srb-mediator. Deletion of PAF1 or CTR9 causes severe pleiotropic phenotypes; deletion of LEO1 or RTF1 suppresses many paf1Δ phenotypes (e.g., restoring CLN1 expression), indicating Paf1 complex integrity is required for normal transcription. Tandem affinity purification, mass spectrometry, genetic double-mutant analysis, gene expression assays Molecular and cellular biology High 11884586
2004 The yeast Paf1 complex (Paf1, Ctr9, Cdc73, Rtf1, Leo1) travels with Pol II on chromatin at promoters and coding regions of active genes. Loss of Paf1 reduces Pol II Ser2 phosphorylation and shortens poly(A) tails. Loss of Rtf1 or Cdc73 dissociates the Paf1 complex from Pol II and chromatin, yet remaining complex members stay stably associated with each other. The major functions of Paf1 can therefore operate independently of actively transcribing Pol II. Chromatin immunoprecipitation (ChIP), functional tagging, poly(A) tail analysis, fractionation Molecular cell High 15149594
2005 Human PAF1 physically interacts with the tumor suppressor parafibromin (HRPT2 product) and with LEO1 and CTR9, forming a complex that also associates with Ser5- and Ser2-phosphorylated forms of the RNA Pol II large subunit CTD. This interaction depends on a C-terminal domain of parafibromin deleted in ~80% of clinically relevant mutations. Co-immunoprecipitation, RNAi knockdown, co-localization Molecular and cellular biology High 15923622
2006 Drosophila Paf1 colocalizes with phosphorylated (actively transcribing) Pol II on polytene chromosomes and is recruited to activated heat shock genes. RNAi depletion of Paf1 impairs Hsp70 RNA induction, reduces trimethylation of histone H3K4 at the Hsp70 promoter, and significantly decreases recruitment of chromatin factors Spt6 and FACT, revealing a role for Paf1 in modulating chromatin structure during active transcription. RNAi, chromatin immunoprecipitation (ChIP), immunofluorescence on polytene chromosomes, RNA assay Molecular and cellular biology High 16354696
2008 The Paf1 complex directly interacts with the cleavage and polyadenylation factor Cft1. This interaction normally requires the Pol II-associated form of Paf1C; when Paf1C is dissociated from Pol II (by loss of Rtf1 or Cdc73), a direct Cft1–Paf1C interaction becomes detectable. Loss of Paf1, Ctr9, Cdc73, or Rtf1 reduces Pol II Ser2 phosphorylation and increases read-through of a polyadenylation site, supporting a role for Paf1C in recruiting 3'-end processing factors. Co-immunoprecipitation, functional tagging, polyadenylation read-through assay, Pol II CTD phosphorylation assay Eukaryotic cell High 18469135
2009 PAF1/PD2 (the human homolog of Paf1) is overexpressed in mouse embryonic stem cells (ESCs), interacts physically with Oct3/4 and RNA Pol II, and is required for maintenance of ESC self-renewal. Knockdown or knockout of PAF1 reduces Oct3/4, SOX2, Nanog, and Shh levels, increases apoptosis, decreases S-phase fraction, and promotes endodermal differentiation markers. Co-immunoprecipitation, siRNA/shRNA knockdown, knockout ESCs, flow cytometry, gene expression analysis Stem cells Medium 19821493
2011 PAF1 (hPaf1/PD2) knockdown in pancreatic cancer cells reduces di- and tri-methylation of histone H3K4. PAF1 colocalizes with the H3K4 methyltransferase MLL1; reduction of PAF1 decreases MLL1 expression and reduces nuclear localization of the chromatin remodeling enzyme CHD1 (which reads H3K4me2/3 marks). PAF1 physically interacts with CHD1, and ectopic PAF1 expression rescues CHD1 nuclear localization, demonstrating PAF1 regulation of chromatin remodeling via H3K4 methylation. siRNA knockdown, Co-immunoprecipitation, confocal co-localization, micrococcal nuclease digestion, Western blot PloS one Medium 22046413
2013 The crystal structure of the human PAF1/LEO1 subcomplex reveals a tightly associated heterodimer formed through antiparallel beta-sheet interactions. LEO1 associates with the PAF1 complex through PAF1, and CTR9 is the key scaffold protein for overall PAF1C assembly. The PAF1/LEO1 heterodimer binds histone H3, the histone octamer, and the nucleosome in vitro. X-ray crystallography, biochemical binding assays (pull-down with histones/nucleosomes), deletion analysis Nucleic acids research High 24038468
2014 H2B K34 ubiquitylation by the MOF-MSL complex acts in early transcription elongation. PAF1, MSL, and RNF20/40 complexes are recruited and stabilized at active gene promoters through direct binary interactions. These complexes regulate chromatin association of pTEFb through a positive feedback loop, facilitating Pol II transition during early elongation. Co-immunoprecipitation (binary interactions), ChIP-seq, siRNA knockdown, RNA Pol II processivity assay Molecular cell Medium 24837678
2015 PAF1 possesses an evolutionarily conserved function in metazoans in regulating RNA Pol II promoter-proximal pausing. Reduction in PAF1 levels leads to increased release of paused Pol II into gene bodies at thousands of genes, increased nascent and mature transcripts, and increased Pol II CTD Ser2 phosphorylation. This is mechanistically explained by increased recruitment of the Ser2-kinase super elongation complex (SEC) upon PAF1 depletion. siRNA depletion, GRO-seq (global run-on sequencing), ChIP-seq, RNA-seq Cell High 26279188
2015 The Paf1 complex (Paf1C) in fission yeast prevents RNAi-directed heterochromatin formation by promoting efficient transcription termination and rapid release of nascent RNA from the site of transcription. In Paf1C mutants, synthetic hairpin RNA can trigger stable, heritable heterochromatin at homologous loci through secondary siRNA production. Compromised transcription termination is sufficient to initiate bistable heterochromatin, but impairment of both termination and nascent transcript release is required for stability. Genetic screen, heterochromatin reporter assays, RNA-seq, ChIP, epistasis analysis in fission yeast Nature High 25807481
2015 Leo1 and Paf1 (subcomplex of PAF1C) are required to prevent spreading of heterochromatin into euchromatin in fission yeast. Loss of Leo1 decreases nucleosome turnover, leading to heterochromatin stabilization at facultative heterochromatin loci, in an RNAi-independent manner. Random mutagenesis screen, ChIP-exo (genome-wide H3K9me2 mapping), histone turnover assay EMBO reports Medium 26518661
2017 PAF1 occupies transcriptional enhancers and restrains hyperactivation of a subset of them. PAF1 loss leads to enhancer activation, which in turn releases Pol II from paused promoters of nearby PAF1 target genes. Knockout of PAF1-regulated enhancers attenuates release of paused Pol II from cognate promoters without major effects on pausing establishment. ChIP-seq, CRISPR enhancer knockout, GRO-seq, nascent RNA assays Science High 28860207
2017 Paf1 level on Pol II varies between genes, is dynamically controlled via promoters by environmental factors, and correlates with levels of transcript processing and export factors on the encoded RNA. High Paf1 levels on Pol II promote nuclear export of transcripts, while low levels correlate with nuclear retention. Loss of Paf1 causes marked transcription elongation defects, but low levels are sufficient for elongation. Native elongating transcript sequencing (NET-seq), strand-specific nucleotide-resolution RNA analysis, yeast genetics Molecular cell High 28190769
2017 Drosophila PAF1 antagonizes PIWI/piRNA-directed gene silencing. PAF1 knockdown enhances PIWI silencing of reporters when piRNAs target transcript regions proximal to the promoter. Loss of PAF1 suppresses endogenous transposable element transcript maturation, suggesting PAF1 acts mechanistically downstream of initial PIWI silencing events in a manner conserved with fission yeast Paf1C opposing AGO1/siRNA silencing. RNAi in Drosophila OSS cells, piRNA-targeted reporter assay, transposable element expression analysis Current biology Medium 28844648
2018 PAF1 interacts with PHF5A and DDX3 in pancreatic cancer stem cells (CSCs), independently of its role as a PAF1 complex (PAF1C) component. The PAF1-PHF5A-DDX3 sub-complex binds to the promoter of Nanog and regulates stemness gene expression. Knockdown of PAF1 reduces CSC markers (NANOG, SOX9, β-CATENIN, CD44v6, ALDH1), tumor sphere formation, and orthotopic tumor growth. DDX3 inhibitor RK-33 reduces PAF1-DDX3-Nanog promoter binding and CSC self-renewal. Co-immunoprecipitation, mass spectrometry, ChIP-seq, CRISPR/Cas9 KO, shRNA KD, orthotopic tumor model, flow cytometry Gastroenterology Medium 32781084
2018 Crystal structures of both human and yeast Ctr9/Paf1 subcomplexes reveal heterodimers with similar conformations, with an interface between the tetratricopeptide repeat (TPR) module of Ctr9 and Paf1. Formation of the Ctr9/Paf1 heterodimer is required for Paf1C assembly and yeast viability. Disruption of the Ctr9-Paf1 interaction greatly reduces histone H3 methylation in vivo. X-ray crystallography (human and yeast), biochemical assembly assays, yeast viability assays, histone modification analysis in vivo Nature communications High 30228257
2019 PAF1C (specifically Paf1 and Leo1 subunits) selectively promotes transcription of long, toxic GGGGCC repeat expansions (≥30 repeats) in C9orf72-associated FTD/ALS but not shorter, nontoxic repeats in Drosophila. PAF1C depletion reduces both repeat RNA and GR dipeptide production. LEO1 binds C9+ repeat chromatin in human C9+ FTD cells, and PAF1C is upregulated following long repeat expression. Drosophila genetic screen (unbiased), RNA quantification, ChIP (LEO1 binding to C9+ chromatin), transgenic models Nature neuroscience Medium 31110321
2019 The Paf1 complex (Paf1C) acts as a transcriptional repressor of ATG32 in yeast, suppressing mitophagy under glucose-rich conditions. Deletion of PAF1 or CTR9 increases ATG32 and ATG11 expression and facilitates mitophagy. Paf1C binds the ATG32 promoter; glucose starvation triggers dissociation of Paf1C from ATG32, de-repressing it. This mitophagic role is independent of Paf1C's positive regulatory functions and is conserved in mammals. ChIP (Paf1C binding to ATG32 promoter), gene deletion, RT-qPCR, mitophagy assays, mammalian validation Autophagy Medium 31525119
2021 Dengue virus NS5 physically interacts with PAF1C (requiring NS5 nuclear localization and the C-terminal region of its methyltransferase domain) and antagonizes PAF1C recruitment to immune response genes. PAF1 knockout enhances DENV2 virion production. PAF1 is required for expression of STAT2-independent immune response genes, defining a distinct antiviral pathway. Co-immunoprecipitation, NS5 mutant analysis, PAF1 CRISPR KO, RNA-seq, viral titer assay PLoS pathogens Medium 34797876
2022 PAF1 governs Pol II promoter-proximal pausing partially by recruiting Integrator-PP2A (INTAC) complex. Acute PAF1 degradation (using rapid degron system) causes most destabilized Pol II to undergo effective release, resulting from skewed balance between INTAC and P-TEFb and leading to hyperphosphorylated SPT5. PAF1 also ensures productive elongation progression. PAF1 degradation causes cumulative decline in histone modifications, further influencing transcriptional output. Rapid degron system (acute degradation), ChIP-seq, GRO-seq, mass spectrometry, phospho-proteomics Science advances High 35363521
2022 PAF1C promotes 3' processing (cleavage and termination) of pervasive transcripts (eRNAs and PROMPTs) by facilitating Integrator complex recruitment to sites of pervasive transcript cleavage 1-3 kb downstream of TSSs. PAF1C also recruits Integrator to coding genes but dissociates from Integrator upon entry into processive elongation. PAF1C depletion (siRNA/degradation), PRO-seq, ChIP-seq, co-immunoprecipitation Cell reports Medium 35294889
2023 The Rtf1 subunit of Paf1C directly interacts with the highly conserved N-terminal helix of the ubiquitin conjugase Rad6 through Rtf1's histone modification domain (HMD). This interaction stimulates H2B K123 ubiquitylation (H2BK123ub) in vivo and in vitro. Separation-of-function RAD6 mutations that impair the Rad6-HMD interface greatly reduce H2BK123ub but not other Rad6 functions, and yield transcriptome profiles matching an H2B ubiquitylation site mutant. In vitro cross-linking/mass spectrometry (interaction mapping), in vitro ubiquitylation assay, yeast genetics (separation-of-function mutants), RNA-seq, in vivo protein cross-linking Proceedings of the National Academy of Sciences of the United States of America High 37216505
2012 Paf1C in Saccharomyces cerevisiae is broadly required for snoRNA 3'-end formation, functioning with RNA-binding proteins Nrd1 and Nab3. Regulation is locus-specific: different Paf1-dependent histone modifications (H2B monoubiquitylation via Rad6, H3K36me2 via Set2) are required at different snoRNA loci. At some snoRNAs, Rad6 function in 3'-end formation is largely independent of its H2B ubiquitylation activity. High-density tiling arrays (transcriptome-wide), ChIP, genetic deletions, epistasis Molecular and cellular biology Medium 23109428

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Infernal 1.1: 100-fold faster RNA homology searches. Bioinformatics (Oxford, England) 2652 24008419
2010 Interleukin-1 (IL-1) pathway. Science signaling 778 20086235
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2012 Atrogin-1, MuRF-1, and sarcopenia. Endocrine 301 22815045
2000 PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding. Blood 294 11023493
1998 Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Molecular and cellular biology 283 9819428
2000 GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. Blood 279 10753833
2002 The Paf1 complex physically and functionally associates with transcription elongation factors in vivo. The EMBO journal 267 11927560
2004 Dial 9-1-1 for DNA damage: the Rad9-Hus1-Rad1 (9-1-1) clamp complex. DNA repair 257 15279787
2004 Transferrin receptor 1. The international journal of biochemistry & cell biology 245 15313461
2010 (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. Journal of immunology (Baltimore, Md. : 1950) 224 20421639
2010 The Paf1 complex: platform or player in RNA polymerase II transcription? Biochimica et biophysica acta 213 20060942
2002 Ctr9, Rtf1, and Leo1 are components of the Paf1/RNA polymerase II complex. Molecular and cellular biology 206 11884586
2015 PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II. Cell 197 26279188
1998 Interleukin-1. The international journal of biochemistry & cell biology 176 9785472
2010 CaV2.1 channelopathies. Pflugers Archiv : European journal of physiology 175 20204399
2005 The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Molecular and cellular biology 154 15923622
2009 CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell 149 19804759
2004 The Paf1 complex has functions independent of actively transcribing RNA polymerase II. Molecular cell 149 15149594
2009 Thyroid transcription factor-1 (TTF-1/Nkx2.1/TITF1) gene regulation in the lung. Clinical science (London, England : 1979) 145 19037882
2004 Expression of Notch-1 and its ligand Jagged-1 in rat liver during liver regeneration. Hepatology (Baltimore, Md.) 141 15057910
1998 Role of PU.1 in hematopoiesis. Stem cells (Dayton, Ohio) 136 9474745
2017 Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation. Trends in biochemical sciences 130 28870425
2014 HIV-1 uncoating is facilitated by dynein and kinesin 1. Journal of virology 115 25231297
2006 Drosophila Paf1 modulates chromatin structure at actively transcribed genes. Molecular and cellular biology 108 16354696
2001 Phenotypic spectrum of mutations in DAX-1 and SF-1. Molecular and cellular endocrinology 105 11738790
2017 PAF1 regulation of promoter-proximal pause release via enhancer activation. Science (New York, N.Y.) 101 28860207
2014 MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation. Nature structural & molecular biology 98 25306110
2008 Kv7.1 (KCNQ1) properties and channelopathies. The Journal of physiology 96 18174212
2015 Regulation of IGF -1 signaling by microRNAs. Frontiers in genetics 95 25628647
2015 The Paf1 complex represses small-RNA-mediated epigenetic gene silencing. Nature 85 25807481
2002 Neurofibromatosis 1. Neurologic clinics 84 12432832
2021 The Paf1 Complex: A Keystone of Nuclear Regulation Operating at the Interface of Transcription and Chromatin. Journal of molecular biology 83 33811920
2015 Using CellMiner 1.6 for Systems Pharmacology and Genomic Analysis of the NCI-60. Clinical cancer research : an official journal of the American Association for Cancer Research 83 26048278
2014 H2B ubiquitylation promotes RNA Pol II processivity via PAF1 and pTEFb. Molecular cell 82 24837678
2008 Interleukin-1 regulates the expression of sphingosine kinase 1 in glioblastoma cells. The Journal of biological chemistry 81 19074142
2012 1q21.1 Microduplication expression in adults. Genetics in medicine : official journal of the American College of Medical Genetics 79 23018752
2018 Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1. Gastroenterology 78 29864419
2014 Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour. Nature communications 76 25099282
2008 Direct interactions between the Paf1 complex and a cleavage and polyadenylation factor are revealed by dissociation of Paf1 from RNA polymerase II. Eukaryotic cell 76 18469135
2002 Microbial dehalorespiration with 1,1,1-trichloroethane. Science (New York, N.Y.) 75 12411705
2017 An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1. Journal of virology 74 28794034
1999 Thrombospondin-1, PECAM-1, and regulation of angiogenesis. Histology and histopathology 73 9987673
2001 Regulation of BOB.1/OBF.1 stability by SIAH. The EMBO journal 72 11483518
2002 Expression of nicotinamide N-methyltransferase (E.C. 2.1.1.1) in the Parkinsonian brain. Journal of neuropathology and experimental neurology 71 11853016
2023 Rapid Access to 2-Substituted Bicyclo[1.1.1]pentanes. Journal of the American Chemical Society 68 36696089
2015 The Paf1 complex factors Leo1 and Paf1 promote local histone turnover to modulate chromatin states in fission yeast. EMBO reports 68 26518661
2019 Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD. Nature neuroscience 65 31110321
2020 RNA Polymerase II-Associated Factor 1 Regulates Stem Cell Features of Pancreatic Cancer Cells, Independently of the PAF1 Complex, via Interactions With PHF5A and DDX3. Gastroenterology 59 32781084
2013 Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes. Journal of the American Society of Nephrology : JASN 57 24029427
2013 Structural insights into Paf1 complex assembly and histone binding. Nucleic acids research 56 24038468
2018 Nedd4-Binding Protein 1 and TNFAIP3-Interacting Protein 1 Control MHC-1 Display in Neuroblastoma. Cancer research 54 30213788
2000 PU.1 expression in microglia. Journal of neuroimmunology 52 10713349
2021 Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. The Journal of experimental medicine 51 33951726
1999 Association of Pur alpha and E2F-1 suppresses transcriptional activity of E2F-1. Oncogene 51 10597240
2008 APE1/Ref-1 regulates PTEN expression mediated by Egr-1. Free radical research 50 18324520
2004 Predicting genes expressed via -1 and +1 frameshifts. Nucleic acids research 50 15371551
2002 TGF beta-1 downregulates DMP-1 and DSPP in odontoblasts. Connective tissue research 50 12489180
2017 Paf1 Has Distinct Roles in Transcription Elongation and Differential Transcript Fate. Molecular cell 49 28190769
2007 Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes. Journal of immunology (Baltimore, Md. : 1950) 49 18056379
2022 PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling. Nature communications 48 35624087
2020 Skeletal muscle CaV1.1 channelopathies. Pflugers Archiv : European journal of physiology 48 32222817
2022 Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1. Science advances 47 35363521
2009 RNA polymerase II associated factor 1/PD2 maintains self-renewal by its interaction with Oct3/4 in mouse embryonic stem cells. Stem cells (Dayton, Ohio) 47 19821493
2001 p21Cip-1/SDI-1/WAF-1 gene is involved in chondrogenic differentiation of ATDC5 cells in vitro. The Journal of biological chemistry 44 11406616
2019 Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension. Arteriosclerosis, thrombosis, and vascular biology 42 31092016
2011 The PAF1 complex differentially regulates cardiomyocyte specification. Developmental biology 42 21338598
2008 Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing hormone stimulated gonadotrophs. Journal of cellular biochemistry 41 18814180
2022 On-DNA Hydroalkylation to Introduce Diverse Bicyclo[1.1.1]pentanes and Abundant Alkyls via Halogen Atom Transfer. Journal of the American Chemical Society 39 35759692
2014 miRNA-1 regulates endothelin-1 in diabetes. Life sciences 39 24394957
1999 DAX-1, an 'antitestis' gene. Cellular and molecular life sciences : CMLS 39 10412368
2019 Reactions of 2-Aryl-1,3-Dithianes and [1.1.1]Propellane. Angewandte Chemie (International ed. in English) 38 31291500
2018 Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation. Nature communications 38 30228257
1995 An overview of the toxicology of HFA-134a (1,1,1,2-tetrafluoroethane). Human & experimental toxicology 37 8579881
2000 Gab-1-mediated IGF-1 signaling in IRS-1-deficient 3T3 fibroblasts. The Journal of biological chemistry 36 10744748
2018 PD2/PAF1 at the Crossroads of the Cancer Network. Cancer research 35 29311159
1977 pD2-, pA2- and pD2'-values of a series of compounds in a histaminic and a cholinergic system. European journal of pharmacology 35 19265
2012 The 1-1-1 fallacy. Immunological reviews 32 22500837
2025 Neutralization and spike stability of JN.1-derived LB.1, KP.2.3, KP.3, and KP.3.1.1 subvariants. mBio 30 40136024
2022 The PAF1 complex promotes 3' processing of pervasive transcripts. Cell reports 29 35294889
2019 The Paf1 complex transcriptionally regulates the mitochondrial-anchored protein Atg32 leading to activation of mitophagy. Autophagy 29 31525119
2018 Translocation and activation of sphingosine kinase 1 by ceramide-1-phosphate. Journal of cellular biochemistry 28 30444039
2013 Enhanced expression of transferrin receptor 1 contributes to oncogenic signalling by sphingosine kinase 1. Oncogene 28 24276247
2011 Subtype specific elevated expression of hyaluronidase-1 (HYAL-1) in epithelial ovarian cancer. PloS one 28 21695196
2021 Nuclear dengue virus NS5 antagonizes expression of PAF1-dependent immune response genes. PLoS pathogens 27 34797876
1996 Molecular analysis of the lissencephaly gene 1 (LIS-1) in medulloblastomas. Neuropathology and applied neurobiology 27 8804025
2014 PD2/Paf1 depletion in pancreatic acinar cells promotes acinar-to-ductal metaplasia. Oncotarget 26 24947474
2011 Human RNA polymerase II-association factor 1 (hPaf1/PD2) regulates histone methylation and chromatin remodeling in pancreatic cancer. PloS one 26 22046413
2017 LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting LRP2BP. Immunology and cell biology 25 29363163
2011 9-1-1: PCNA's specialized cousin. Trends in biochemical sciences 25 21978893
2024 Neutralization and Stability of JN.1-derived LB.1, KP.2.3, KP.3 and KP.3.1.1 Subvariants. bioRxiv : the preprint server for biology 24 39282390
2023 Paf1 complex subunit Rtf1 stimulates H2B ubiquitylation by interacting with the highly conserved N-terminal helix of Rad6. Proceedings of the National Academy of Sciences of the United States of America 24 37216505
2012 Effects of the Paf1 complex and histone modifications on snoRNA 3'-end formation reveal broad and locus-specific regulation. Molecular and cellular biology 24 23109428
2009 PU.1 activation relieves GATA-1-mediated repression of Cebpa and Cbfb during leukemia differentiation. Molecular cancer research : MCR 24 19825991
2017 Tex19.1 promotes Spo11-dependent meiotic recombination in mouse spermatocytes. PLoS genetics 23 28708824
2014 PDX-1 (pancreatic/duodenal homeobox-1 protein 1). Pathologica 23 25845046
2017 An Apple Protein Kinase MdSnRK1.1 Interacts with MdCAIP1 to Regulate ABA Sensitivity. Plant & cell physiology 22 29016962
2017 Drosophila PAF1 Modulates PIWI/piRNA Silencing Capacity. Current biology : CB 21 28844648
2021 Maresin-1 induces cardiomyocyte hypertrophy through IGF-1 paracrine pathway. American journal of physiology. Cell physiology 20 34038245
2016 Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma. Oncotarget 20 26689992

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