Affinage

YY1

Transcriptional repressor protein YY1 · UniProt P25490

Length
414 aa
Mass
44.7 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YY1 is a multifunctional zinc-finger transcription factor that serves as a structural organizer of enhancer-promoter chromatin loops and a context-dependent transcriptional activator or repressor. YY1 dimerizes and oligomerizes to bridge enhancers and promoters in a cohesin-independent manner, with some loops requiring YY1 specifically at mitotic exit for re-establishment (PMID:29224777, PMID:39210046); it also functions as a bivalent RNA-DNA adaptor that tethers Xist RNA to the inactive X chromosome to initiate X-chromosome inactivation (PMID:21729784). Its transcriptional output is determined by lineage-specific partners—recruiting HDAC1 to repress differentiation inhibitors in oligodendrocyte progenitors (PMID:17640524), cooperating with MITF in melanocytes (PMID:22570637), competing with the Notch co-activator MAML1 for RBPJ binding in endothelial cells (PMID:32075915), and recruiting PRC1 via YAF2/RYBP and PRC2 via EZH2 for Polycomb-mediated silencing (PMID:24285299, PMID:34065631)—while its activity is extensively regulated by post-translational modifications including Src-mediated Y383 phosphorylation that inhibits DNA/RNA binding (PMID:26198631), CK2α-mediated S118 phosphorylation that promotes atherosclerosis (PMID:34747636), p300-mediated K183 lactylation that enhances chromatin binding (PMID:37085894), and Smurf2/OTUD3-controlled ubiquitin-proteasome turnover (PMID:24803334, PMID:38351178). De novo heterozygous YY1 mutations cause a neurodevelopmental syndrome characterized by global loss of YY1 chromatin occupancy and H3K27 acetylation at enhancers (PMID:28575647).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    The discovery that YY1 physically associates with c-Myc—which inhibits both YY1's activator and repressor functions—established that YY1 is not an autonomous switch but a partner-dependent transcription factor whose output is modulated by oncoproteins.

    Evidence Yeast two-hybrid, affinity chromatography, and cotransfection reporter assays in mammalian cells

    PMID:8266081

    Open questions at the time
    • Structural basis of c-Myc–YY1 interaction unknown
    • Which YY1 target genes are regulated by c-Myc modulation not defined
  2. 1995 High

    Identification of YY1 as a nuclear matrix protein (NMP-1) associated with residual nucleoli, and the finding that immunophilins CyPA and FKBP12 interact with YY1 and modulate its transcriptional activity, revealed that YY1 functions within a defined subnuclear scaffold and is subject to regulation by peptidyl-prolyl isomerases.

    Evidence Nuclear matrix fractionation, gel-shift, in situ immunofluorescence (NMP-1); yeast two-hybrid, mammalian Co-IP, pharmacological disruption with CsA/FK506 (immunophilins)

    PMID:7479833 PMID:7541038

    Open questions at the time
    • Physiological relevance of immunophilin–YY1 interaction in vivo not established
    • Whether CyPA/FKBP12 catalytically isomerize YY1 not tested
  3. 2004 High

    Genetic epistasis in Drosophila demonstrated that CtBP is required for YY1 (Pho) DNA binding in vivo and for subsequent Polycomb group protein recruitment and histone modification, establishing the first essential cofactor for YY1-mediated Polycomb silencing.

    Evidence Drosophila CtBP mutant analysis, ChIP for PcG occupancy and histone marks

    PMID:15520279

    Open questions at the time
    • Mechanism by which CtBP unmasks YY1 DNA binding not resolved
    • Whether CtBP dependence is conserved in mammalian PcG targeting not shown
  4. 2007 High

    Conditional YY1 knockout in the oligodendrocyte lineage revealed that YY1 recruits HDAC1 to repress differentiation inhibitors Tcf4 and Id4, establishing YY1 as a lineage-specific differentiation regulator, while identification of K288 sumoylation by PIASy showed that SUMO modification stabilizes YY1 and modulates its transcriptional output in a promoter-dependent manner.

    Evidence Conditional KO with myelination phenotype, ChIP/Co-IP for HDAC1 (oligodendrocytes); in vitro sumoylation, K288R mutagenesis, reporter assays (sumoylation)

    PMID:17353273 PMID:17640524

    Open questions at the time
    • Whether sumoylation alters YY1-HDAC1 interaction not tested
    • Full repertoire of YY1 target genes in OPC differentiation not mapped
  5. 2008 Medium

    Systematic motif and zinc-finger mutagenesis extended YY1's DNA recognition to a longer consensus (GCCGCCATTTTG) requiring the first zinc finger, refining the understanding of how YY1 selects genomic targets.

    Evidence EMSA with systematic DNA motif variants and zinc-finger substitution mutants

    PMID:18950698

    Open questions at the time
    • In vivo validation of the extended motif's functional significance not provided
    • Contribution of flanking sequence context to binding affinity not addressed
  6. 2009 Medium

    Two studies revealed YY1's role in epigenetic memory: YY1 binding sites in DMRs of Peg3 and Xist are required for de novo DNA methylation during oogenesis, and YY1 autoregulates its own transcription through intronic binding sites, demonstrating both trans-regulatory imprinting control and a self-buffering feedback loop.

    Evidence Conditional YY1 KD during oogenesis/spermatogenesis with bisulfite sequencing; inducible overexpression with reporter mutagenesis

    PMID:19628663 PMID:19712462

    Open questions at the time
    • Whether YY1 recruits specific DNMTs to DMRs not identified
    • Autoregulation kinetics and quantitative buffering capacity not measured
  7. 2011 High

    Demonstration that YY1 simultaneously binds Xist RNA (via Repeat C) and DNA (via an epigenetically regulated trio of sites) to dock Xist onto the X chromosome nucleation center established YY1 as a bivalent RNA-DNA adaptor critical for X-chromosome inactivation.

    Evidence RNA immunoprecipitation, ChIP, mutational dissection of RNA- and DNA-binding motifs, allele-specific assays

    PMID:21729784

    Open questions at the time
    • Structural basis of simultaneous RNA and DNA binding not resolved
    • Whether YY1 bridges other lncRNAs to chromatin genome-wide not explored
  8. 2012 High

    Conditional YY1 knockout in melanocytes combined with Co-IP and ChIP-seq showed that YY1 physically interacts with the lineage-restricted factor MITF to co-regulate pigmentation genes, explaining how a ubiquitous factor achieves lineage-specific transcriptional output.

    Evidence Melanocyte-specific Yy1 KO, Co-IP of YY1-MITF, ChIP-seq, coat color phenotype

    PMID:22570637

    Open questions at the time
    • Whether YY1-MITF form a stable complex or transient interaction not determined
    • Genome-wide partitioning of MITF-dependent versus -independent YY1 targets not complete
  9. 2013 High

    Two studies clarified YY1's role in Polycomb recruitment and retroviral silencing: YAF2 bridges YY1 to PRC1 in a YY1 DNA-binding-dependent manner, and YY1 binds ERV LTRs in embryonic cells through interaction with Trim28 to recruit repressive histone marks, defining distinct PRC1 and Trim28/KRAB pathways for YY1-mediated silencing.

    Evidence Reciprocal Co-IP, ChIP, siRNA, Drosophila rescue (YAF2-PRC1); LTR binding-site deletion, YY1 depletion, Trim28 Co-IP (ERV silencing)

    PMID:23810560 PMID:24285299

    Open questions at the time
    • Whether YAF2 and Trim28 pathways operate on overlapping or distinct target sets not resolved
    • Structural basis of YAF2-YY1 and Trim28-YY1 interfaces only partially mapped
  10. 2014 High

    YY1 was shown to activate Xist transcription by competing with the repressor REX1 for binding at the Xist promoter, while structural studies revealed YY1 forms bell-shaped dimers that oligomerize and interact with RuvBL1/2 ATPases to participate in homologous recombination, expanding YY1's functions beyond transcription to DNA repair.

    Evidence ChIP, reporter, bisulfite sequencing (Xist activation); electron microscopy, BiFC, EMSA, RAD51 foci assay (oligomers/HR)

    PMID:24990942 PMID:25209548

    Open questions at the time
    • Whether oligomerization is required for enhancer-promoter looping not tested
    • Mechanism of YY1/RuvBL1-2 cooperation in RAD51 loading not defined
  11. 2015 High

    Multiple regulatory mechanisms were defined: Src/EGFR-mediated Y383 phosphorylation inhibits YY1 DNA/RNA binding, Smurf2-mediated ubiquitination targets YY1 for proteasomal degradation, S-nitrosation of zinc-finger cysteines blocks DNA binding, a somatic T372R zinc-finger mutation in insulinomas creates a neomorphic binding specificity activating cAMP/Ca²⁺ signaling genes, and Linc-YY1 evicts YY1/PRC2 from target promoters to promote myogenic differentiation.

    Evidence In vitro kinase assay with Y383 mutagenesis (Src); ubiquitination/CHX chase (Smurf2); S-nitrosation detection and EMSA (NO); exome sequencing with ChIP-seq of WT vs T372R (insulinoma); RIP and ChIP with in vivo muscle regeneration (Linc-YY1)

    PMID:16143308 PMID:24803334 PMID:25787250 PMID:26198631 PMID:26658965

    Open questions at the time
    • Phosphatase(s) reversing Y383 phosphorylation unknown
    • Whether Smurf2 ubiquitinates YY1 at specific lysines not mapped
    • Linc-YY1 mechanism of PRC2 eviction not structurally resolved
  12. 2017 High

    ChIP-seq, Hi-C, and acute protein depletion established YY1 as a general structural regulator of enhancer-promoter loops analogous to CTCF, while patient-derived cells with YY1 haploinsufficiency showed global loss of YY1 chromatin binding and H3K27ac at enhancers, linking YY1 architectural function to a neurodevelopmental syndrome.

    Evidence dTAG depletion, CRISPR deletion of binding sites, 4C-seq, Hi-C (looping); ChIP-seq from cells of 23 patients with de novo YY1 mutations (disease)

    PMID:28575647 PMID:29224777

    Open questions at the time
    • Whether YY1-mediated loops require specific cofactors or are solely dimer-driven not resolved
    • Genotype-phenotype correlations across different YY1 mutations not fully characterized
  13. 2019 High

    Context-specific transcriptional programs were delineated: YY1 represses TGFB1 in renal mesangial cells to protect against diabetic nephropathy, forms an active complex with HIF-1α at VEGF promoters for angiogenesis, and undergoes liquid-liquid phase separation with p300/p65/CEBPB to activate IL-6 enhancer-promoter interactions in M2 macrophages.

    Evidence MS-based DNA-protein screen, ChIP, mouse DN models (TGFB1); Co-IP of YY1-HIF-1α, ChIP at VEGF (angiogenesis); LLPS assay, ChIP-seq, CRISPR KO (phase separation)

    PMID:20660740 PMID:31534017 PMID:37094986

    Open questions at the time
    • Whether phase separation is required for all YY1-dependent enhancer-promoter contacts unknown
    • Structural determinants of YY1 LLPS not defined
  14. 2021 High

    Multiple studies converged on YY1's metabolic and signaling roles: YY1 cooperates with BRD2/4 to activate glycolytic PFKP, YY1's interaction with EZH2 through the OPB domain controls H3K27me3 deposition, PHF8 demethylates YY1 itself to convert it into a co-repressor of ETC genes, CK2α phosphorylates YY1 at S118 to drive endothelial proliferation and atherosclerosis, and YY1 activates SLC7A11 to suppress ferroptosis.

    Evidence ChIP-seq/MS interactome with cis-element mutagenesis (BRD2/4-PFKP); peptide competition, ChIP-seq for H3K27me3 (EZH2); PHF8 KO/inhibitor with YY1 methylation assay (PHF8); phosphoproteomics, S118A transgenic mice (CK2α); competitive ChIP and ferroptosis assays (SLC7A11)

    PMID:33849067 PMID:34065631 PMID:34747636 PMID:35246964 PMID:38165927

    Open questions at the time
    • Specific methylation site(s) on YY1 targeted by PHF8 not identified
    • Whether BRD2/4-YY1 co-occupancy is a general phenomenon across cancer types unclear
    • Direct structural data for YY1-EZH2 OPB/YPB interface lacking
  15. 2023 High

    Identification of p300-mediated lactylation at YY1 K183 that enhances chromatin binding and FGF2 transcription established lactylation as a metabolically responsive PTM tuning YY1 activity, later extended to microglial inflammatory gene regulation in autoimmune uveitis.

    Evidence Mass spectrometry, K183R mutagenesis, ChIP, p300 inhibition in vitro/in vivo (FGF2); CUT&Tag, p300 inhibitor in uveitis model (microglia)

    PMID:37085894 PMID:38493498

    Open questions at the time
    • Delactylase(s) that reverse K183 lactylation not identified
    • Genome-wide scope of lactylation-dependent versus -independent YY1 targets not defined
  16. 2024 High

    Advanced chromatin conformation and acute degradation studies showed that YY1 maintains enhancer-promoter loops independently of cohesin and is partially bookmarked on mitotic chromatin, re-establishing loops at G1 entry; separately, YY1 was identified as a required cofactor for Ngn2-mediated neuronal enhancer activation during astrocyte-to-neuron reprogramming, and OTUD3 was characterized as a PLK1-regulated deubiquitinase stabilizing YY1.

    Evidence dTAG degradation, Hi-C, cell-cycle synchronization, cohesin depletion (looping); single-cell multiomics, Yy1 cKO, Co-IP of YY1-Ngn2 (reprogramming); DUB screen, ubiquitination assay, PLK1 phosphorylation of OTUD3 (stability)

    PMID:38351178 PMID:38956165 PMID:39210046

    Open questions at the time
    • Molecular determinants distinguishing YY1-bookmarked from non-bookmarked sites unknown
    • Whether Ngn2-YY1 cooperation is unique to reprogramming or also operates in developmental neurogenesis not addressed
    • Full ubiquitin site map on YY1 not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis of YY1 simultaneous RNA and DNA binding, (2) how YY1 phase separation, oligomerization, and dimerization relate to each other and to enhancer-promoter loop formation in vivo, (3) the full combinatorial code of post-translational modifications that switch YY1 between activator and repressor states, and (4) whether YY1's cohesin-independent architectural function operates genome-wide or at a specialized subset of loci.
  • No high-resolution structure of YY1 bound simultaneously to RNA and DNA
  • Quantitative in vivo PTM crosstalk map absent
  • Genome-wide assignment of cohesin-dependent versus YY1-dependent loops incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 8 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0005694 chromosome 3
Pathway
R-HSA-74160 Gene expression (Transcription) 10 R-HSA-1266738 Developmental Biology 5 R-HSA-4839726 Chromatin organization 5 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
BRD2BRD4EZH2HDAC1MITFRBPJTRIM28YAF2
Complex memberships
PRC1 (via YAF2/RYBP)PRC2 (via EZH2)Trim28-YY1 silencing complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 YY1 binds to active enhancers and promoter-proximal elements and forms dimers that facilitate structural interactions between enhancers and promoters. Deletion of YY1 binding sites or depletion of YY1 protein disrupts enhancer-promoter looping and gene expression, establishing YY1 as a structural regulator of enhancer-promoter loops analogous to CTCF. ChIP-seq, Hi-C, CRISPR deletion of binding sites, protein depletion with dTAG system, 4C-seq Cell High 29224777
2011 YY1 acts as a bivalent adaptor protein capable of binding both RNA (Xist RNA through Repeat C) and DNA (through an epigenetically regulated trio of YY1 sites on the inactive X), thereby docking Xist particles onto the X chromosome nucleation center to initiate X-chromosome inactivation. RNA immunoprecipitation, ChIP, mutational analysis of YY1 RNA- and DNA-binding motifs, allele-specific assays, deletion of YY1 binding sites Cell High 21729784
1993 YY1 physically associates with c-Myc (but not Max), and c-Myc inhibits both the repressor and activator functions of YY1, establishing c-Myc as a modulator of YY1 transcriptional activity. Yeast two-hybrid screen, affinity chromatography, cotransfection reporter assays Science High 8266081
2007 YY1 acts as a lineage-specific transcriptional repressor in oligodendrocyte progenitors by recruiting histone deacetylase-1 (HDAC1) to the promoters of myelin gene expression inhibitors Tcf4 and Id4, thereby enabling oligodendrocyte progenitor differentiation. Conditional yy1 knockout in oligodendrocyte lineage, ChIP, co-immunoprecipitation, in vivo phenotypic analysis (myelination defects, ataxia) Neuron High 17640524
2014 YY1 activates Xist transcription by binding directly to the Xist 5' region, competing with the Xist repressor REX1; DNA methylation controls mono-allelic fixation of YY1 to the Xist locus at the onset of XCI, establishing YY1 as the first autosomal activating factor in Xist regulation. YY1 loss-of-function, ChIP, luciferase reporter assays, bisulfite sequencing, allele-specific analysis Nature Communications High 25209548
2004 YY1 DNA binding in vivo and its recruitment of Polycomb Group (PcG) proteins to DNA requires CtBP; in a CtBP mutant background, YY1 DNA binding is masked (without protein degradation or nuclear export) and PcG-dependent histone H3 deacetylation and methylation do not occur. Drosophila CtBP mutant genetic analysis, ChIP, histone modification assays, Western blot Genes & Development High 15520279
2013 YY1 interacts with YAF2 (a RYBP homolog); YAF2 bridges YY1 to the PRC1 complex and is responsible for PcG recruitment to DNA, which requires prior YY1 DNA binding. Knockdown of YY1 abrogates PcG recruitment even when YAF2 is exogenously supplied. Co-immunoprecipitation, ChIP in HeLa cells, Drosophila phenotypic rescue, siRNA knockdown Nucleic Acids Research High 24285299
2007 YY1 is sumoylated at lysine 288 by the SUMO E3 ligase PIASy both in vivo and in vitro. PIASy stimulates YY1 sumoylation through its interaction with YY1 (dependent on the PPxY motif in YY1) rather than through its RING finger domain, colocalizes with YY1 in the nucleus, stabilizes YY1, and differentially regulates YY1 transcriptional activity on different promoters. In vitro and in vivo sumoylation assays, mutagenesis of sumoylation site (K288R), PIASy interaction mapping, co-immunoprecipitation, reporter assays Molecular and Cellular Biology High 17353273
1995 Cyclophilin A (CyPA) and FK506-binding protein 12 (FKBP12) specifically interact with YY1 in both yeast and mammalian cells; cyclosporin A and FK506 disrupt these interactions, respectively; overexpression of CyPA and FKBP12 differentially and promoter-dependently alter YY1-regulated transcription. Yeast two-hybrid, co-immunoprecipitation in mammalian cells, pharmacological disruption, cotransfection reporter assays Journal of Biological Chemistry Medium 7541038
2015 YY1 is sumoylated and also subject to ubiquitin-proteasome–mediated degradation by the E3 ubiquitin ligase Smurf2, which interacts with YY1 via its PPxY motif, induces poly-ubiquitination of YY1, and shortens YY1 protein half-life. Smurf2-mediated degradation reduces YY1 transcriptional activity and relieves YY1-mediated suppression of p53. Co-immunoprecipitation, ubiquitination assay, cycloheximide chase (half-life), Smurf2 knockdown, reporter assays Biochimica et Biophysica Acta Medium 24803334
2005 Nitric oxide (NO) inhibits YY1 DNA-binding activity through S-nitrosation of YY1 (detected at cysteine residues coordinated by Zn2+ in the zinc finger domain), which leads to upregulation of Fas expression and sensitization of prostate cancer cells to Fas-induced apoptosis. EMSA, S-nitrosation detection by DAN-based fluorometry and anti-SNO immunoprecipitation, siRNA knockdown of YY1, immunofluorescence Biochemical and Biophysical Research Communications Medium 16143308
2015 YY1 is phosphorylated at multiple tyrosine residues by Src family kinases in vitro and in vivo; phosphorylation at tyrosine 383 specifically interferes with YY1 DNA and RNA binding, downregulating YY1 transcriptional activity. YY1 is also identified as a downstream target of EGFR signaling. Pharmacological inhibition, kinase overexpression, kinase knockout, site-directed mutagenesis (Y383), EMSA, in vitro kinase assay, reporter assays Journal of Biological Chemistry High 26198631
1995 The nuclear matrix protein NMP-1 is identical to YY1; YY1/NMP-1 is localized in the nuclear matrix (principally associated with residual nucleoli) and binds sequence-specifically to histone H4 gene site IV, suggesting YY1 mediates gene-matrix interactions. Gel-shift assay, Western blot with YY1 antibody, nuclear matrix fractionation, in situ immunofluorescence, reconstitution with purified YY1 PNAS High 7479833
2014 YY1 assembles into homo-oligomeric species built from a bell-shaped dimer (characterized by electron microscopy and bimolecular fluorescence complementation in vivo); these oligomers bind DNA substrates without canonical YY1 consensus sequences in vitro, and DNA binding is enhanced by interaction with RuvBL1-RuvBL2 AAA+ ATPases (YY1 interacts preferentially with RuvBL1). YY1 and RuvBL2 ATPase activity are required for RAD51 foci formation during homologous recombination. Electron microscopy, bimolecular fluorescence complementation, EMSA, co-immunoprecipitation, RAD51 foci assay Journal of Biological Chemistry Medium 24990942
2015 YY1 binds directly to the promoter of Linc-YY1, and Linc-YY1 interacts with YY1 protein through its middle domain to evict YY1/PRC2 complexes from target promoters, activating gene expression in trans and promoting myogenic differentiation. RNA immunoprecipitation, gain/loss-of-function in C2C12 myoblasts and satellite cells, in vivo muscle regeneration assay, ChIP, RNA-protein interaction mapping Nature Communications Medium 26658965
2009 YY1 autoregulates its own transcription through a cluster of YY1-binding sites within the first intron of the YY1 gene; overexpression of exogenous YY1 reduces endogenous YY1 transcription, and reverting to normal YY1 levels restores endogenous transcription, establishing YY1 as the first known autoregulating transcription factor in mammalian genomes. Inducible overexpression cell line, luciferase reporter with site mutations, gel shift assay BMC Molecular Biology Medium 19712462
2013 YY1 binds to the LTR region of exogenous and endogenous retroviruses (ERVs) in embryonic cells and is required for their transcriptional silencing; deletion of the YY1-binding site causes major loss of silencing and loss of repressive histone marks. YY1 physically interacts with Trim28 in an embryonic cell–specific manner. ChIP, LTR binding site deletion, YY1 depletion (siRNA/shRNA), RT-qPCR of ERV expression, co-immunoprecipitation Cell Reports High 23810560
2018 Characterization of Trim28-YY1 interaction domains: the RBCC domain of Trim28 is sufficient for interaction with YY1, and the acidic region 1 and zinc fingers of YY1 are necessary and sufficient for interaction with Trim28. Sumoylation and phosphorylation of Trim28 regulate M-MLV silencing, with residue K779 of Trim28 critical for silencing in embryonic cells. Domain mapping by deletion constructs, co-immunoprecipitation, retroviral silencing reporter assays Virology Medium 29407374
2023 YY1 is lactylated at lysine 183 (K183) by the writer p300; hyperlactylation at K183 directly enhances YY1 binding to the FGF2 promoter and increases FGF2 transcription, promoting angiogenesis. YY1 K183 mutation abolishes these effects. Mass spectrometry identification of lactylation sites, K183R mutagenesis, ChIP, luciferase reporter, p300 inhibitor (A485) in vitro and in vivo, p300 overexpression Genome Biology High 37085894
2024 YY1 is also lactylated by p300 at retinal microglia during autoimmune uveitis; YY1 lactylation promotes microglial activation and transcription of inflammatory genes including STAT3, CCL5, IRF1, IDO1, and SEMA4D as shown by CUT&Tag analysis. p300 inhibition decreases YY1 lactylation and suppresses microglial inflammation. CUT&Tag sequencing, p300 inhibitor treatment, lactylation inhibition, in vivo autoimmune uveitis model, Co-IP Advanced Science Medium 38493498
2015 Somatic T372R mutation in the DNA-binding zinc finger of YY1 (found in 14/43 insulinomas) changes the DNA motif recognized by YY1, leading to neo-morphic activation of ADCY1 and CACNA2D2, genes involved in cAMP and Ca2+ signaling that regulate insulin secretion. Exome sequencing, ChIP-seq comparing wild-type and T372R YY1, expression of mutant in INS-1 cells, insulin secretion assay PNAS High 25787250
2017 YY1 haploinsufficiency in humans with de novo YY1 mutations/deletions leads to global loss of YY1 chromatin binding with preferential retention at high-occupancy sites, and a widespread loss of H3K27 acetylation particularly at YY1-bound enhancers, defining a clinical syndrome caused by dysregulation of key transcriptional regulators. ChIP with antibodies against both ends of YY1 from patient cells, H3K27ac ChIP-seq, clinical genomics of 23 individuals American Journal of Human Genetics High 28575647
2018 YY1 directly activates transcription of G6PD (glucose-6-phosphate dehydrogenase), the rate-limiting enzyme of the pentose phosphate pathway, in a p53-independent manner, thereby promoting nucleotide synthesis, NADPH production, ROS reduction, and tumor cell proliferation. ChIP, luciferase reporter assay with G6PD promoter, siRNA knockdown, metabolic assays (NADPH, nucleotide synthesis), xenograft tumor model Cancer Research Medium 29921695
2020 Endothelial YY1 deletion in mice causes embryonic lethality and impairs sprouting angiogenesis; mechanistically, YY1 binds the N-terminal domain of RBPJ and competes with MAML1 for RBPJ binding, thereby blocking NICD/MAML1/RBPJ complex formation and repressing Notch-dependent gene expression to control endothelial tip cell fate. EC-specific conditional knockout mice, retinal angiogenesis assay, aortic ring assay, co-immunoprecipitation of YY1-RBPJ, competition assay with MAML1, Notch target gene expression analysis PNAS High 32075915
2021 YY1 co-occupies gene-regulatory elements with bromodomain-containing proteins BRD2/4 in prostate cancer; YY1 directly binds and activates PFKP (phosphofructokinase, platelet type), the rate-limiting enzyme for glycolysis, establishing a YY1:BRD2/4-PFKP oncogenic axis contributing to the Warburg effect. ChIP-seq, interactome profiling (mass spectrometry), gene loss-of-function and rescue, mutagenesis of YY1-bound cis-elements, metabolic assays, xenograft Nucleic Acids Research High 33849067
2021 YY1 physically interacts with EZH2 through a specific 'oncoprotein binding' (OPB) domain on YY1; disruption of the YY1-EZH2 interaction using synthetic peptides targeting either the OPB domain on YY1 or the YY1-protein binding (YPB) domain on EZH2 alters H3K27me3 at hundreds of genomic loci and inhibits breast cancer cell growth. Domain mapping, synthetic peptide competition assay, ChIP-seq (H3K27me3), cell viability, xenograft tumor model Cancers Medium 34065631
2021 PHF8 demethylates YY1 (functioning as a co-repressor of nuclear-encoded ETC genes) to drive mitochondrial ROS production; PHF8 acts as a demethylase not on histones but on the transcription factor YY1 itself to repress ETC gene transcription and promote cancer cell growth. PHF8 KO, PHF8 inhibitor (iPHF8), YY1 methylation assay, ETC gene expression profiling, xenograft and PDX models, genetic ablation PNAS Medium 38165927
2021 CK2α (casein kinase 2α) directly phosphorylates YY1 at serine 118 (S118) in endothelial cells under disturbed/oscillatory flow; phospho-YY1S118 directly binds ZKSCAN4, inducing HDM2 promoter activity and gene expression, which downregulates p53 and p21CIP1 to promote EC proliferation and atherosclerosis. Quantitative phosphoproteomics, in situ proximity ligation assay, yeast two-hybrid for ZKSCAN4 interaction, S118 non-phosphorylatable transgenic mice, luciferase reporter, CK2 inhibitor in ApoE-/- mice Circulation Research High 34747636
2024 OTUD3 is a deubiquitinase for YY1 that stabilizes YY1 protein; PLK1 phosphorylates OTUD3 at S326, enhancing OTUD3 binding to and deubiquitination of YY1, thereby increasing YY1 protein levels and promoting colorectal cancer cell proliferation. DUB screening, co-immunoprecipitation, ubiquitination assay, OTUD3 KD/KO, phosphorylation assay, PLK1 inhibition, clinical CRC tissue analysis Cell Death & Disease Medium 38351178
2009 YY1 binding sites within differentially methylated regions (DMRs) of Peg3 and Xist are required for de novo DNA methylation of these loci during oogenesis; YY1 knockdown during oogenesis causes loss of DNA methylation on Peg3 and Xist DMRs, while YY1 knockdown during spermatogenesis maintains unmethylation status. Conditional YY1 knockdown during oogenesis and spermatogenesis, bisulfite sequencing of DMRs Nucleic Acids Research Medium 19628663
2024 YY1 maintains numerous enhancer-promoter loops in erythroid cells independent of cohesin-mediated loop extrusion; YY1 is partially retained on mitotic chromatin (predominantly at gene promoters) and rapidly rebinds during mitotic exit, coinciding with enhancer-promoter loop re-establishment. Some YY1-dependent loops require YY1 for establishment at G1-phase entry but not for maintenance in interphase, demonstrating cell-cycle stage–dependent architectural function. Acute YY1 degradation (dTAG), Hi-C, ChIP-seq, cell-cycle synchronization, 4C-seq, cohesin depletion comparison Nature Genetics High 39210046
2012 YY1 physically interacts with M-MITF (Waardenburg Syndrome IIA gene product) in melanocytes and cooperates with M-MITF to regulate expression of pigmentation genes including KIT; genome-wide ChIP-seq identified YY1 targets in the melanocyte lineage, demonstrating how a ubiquitous factor (YY1) gains lineage-specific functions through co-regulation with a lineage-restricted factor (M-MITF). Conditional yy1 KO in melanocyte lineage, co-immunoprecipitation of YY1-MITF, ChIP-seq, reporter assays, coat color phenotype analysis PLoS Genetics High 22570637
2008 YY1 recognizes a longer consensus DNA-binding motif (GCCGCCATTTTG) beyond the previously known core sequence, requiring intact contribution of its first zinc finger unit; a three–amino acid substitution mimicking Drosophila Pho in the first zinc finger weakens DNA-binding specificity and shortens the recognized motif to GCCAT. Gel shift assay (EMSA), systematic DNA motif analysis, zinc finger mutagenesis Genomics Medium 18950698
2021 YY1 and YY2 bind competitively to the same DNA-binding site in the SLC7A11 promoter and antagonistically regulate ferroptosis: YY1 activates SLC7A11 to promote glutathione biosynthesis and suppress ferroptosis, while YY2 represses SLC7A11 to induce ferroptosis and suppress tumorigenesis. ChIP, luciferase reporter assay, site-directed mutagenesis of zinc finger domains, siRNA knockdown, ferroptosis assays (lipid peroxidation, cell death), clinical mutation analysis Advanced Science Medium 35246964
2021 3-Hydroxyanthranilic acid (3-HAA), a kynurenine derivative, directly binds YY1 as an agonist ligand, inducing YY1 phosphorylation at Thr398 by PKCζ and enhancing YY1 chromatin binding activity to increase expression of target genes including apoptotic genes in hepatocellular carcinoma. Ligand-binding assay, co-immunoprecipitation, phosphorylation assay, ChIP, cell viability assay Journal of Hematology & Oncology Low 34563230
2019 YY1 forms an active complex with HIF-1α at VEGF gene promoters and increases VEGF transcription; CXCR4/SDF-1 inhibition causes YY1 cytoplasmic accumulation by reducing YY1 phosphorylation through AKT downregulation. Co-immunoprecipitation of YY1-HIF-1α, ChIP at VEGF promoter, RT-PCR, ELISA, in vitro angiogenesis assay, phosphorylation analysis PNAS Medium 20660740
2024 YY1 is recruited by direct protein-protein interaction with Neurogenin2 (Ngn2) to neuronal enhancer sites in astrocyte-to-neuron reprogramming; YY1 deletion impairs activation of neuronal enhancers and genes and reduces reprogramming efficiency without affecting Ngn2 chromatin binding, establishing YY1 as a required co-factor for Ngn2-mediated epigenome remodeling. Single-cell multiomics, ChIP-seq, ATAC-seq, co-immunoprecipitation of YY1-Ngn2, Yy1 conditional deletion, direct neuronal reprogramming assay Nature Neuroscience High 38956165
2019 In M2 macrophages in prostate cancer, YY1 undergoes liquid-liquid phase separation (LLPS) with transcriptional cofactors p300, p65, and CEBPB; the YY1 phase separation complex upregulates IL-6 by promoting IL-6 enhancer-promoter chromatin interactions, facilitating prostate cancer progression. LLPS assay, H3K27ac-ChIP-seq, YY1 ChIP-seq, CRISPR-Cas9 KO, RNA-seq, chromatin interaction assay, transgenic YY1-overexpressing mice Journal for Immunotherapy of Cancer Medium 37094986
2016 GON4L interacts with YY1 and promotes YY1's association with the androgen receptor, forming a GON4L-YY1-androgen receptor complex that drives CD24 expression and cancer cell growth. shRNA library screen, co-immunoprecipitation of GON4L-YY1 and YY1-AR, gene silencing with proliferation/tumor growth assays, clinical tissue analysis Cancer Research Medium 27312530
2019 YY1 directly binds to and represses the TGFB1 promoter in human renal mesangial cells; YY1 overexpression attenuates glomerulosclerosis in mouse DN models, and YY1 knockdown aggravates renal lesions, establishing YY1 as a potent transcriptional repressor of TGFβ1 in diabetic nephropathy. Mass spectrometry-based DNA-protein interaction screen, ChIP, luciferase reporter, in vitro and in vivo YY1 manipulation (knockdown and overexpression), mouse DN models Science Translational Medicine High 31534017
2019 YY1 is a substrate of CARM1-mediated arginine methylation; CARM1 co-activates YY1-mediated reporter gene activation in vivo and the two proteins regulate each other in a positive feedback loop in oral cancer. In vivo arginine methylation assay, reporter assay with CARM1 co-expression, siRNA knockdown, qRT-PCR, xenograft Oncotarget Low 31217904

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell 765 29224777
2006 Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 635 16314846
2011 YY1 tethers Xist RNA to the inactive X nucleation center. Cell 413 21729784
1993 Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc. Science (New York, N.Y.) 259 8266081
2023 YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2. Genome biology 236 37085894
2007 The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron 218 17640524
2015 Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1. Nature communications 161 26658965
1995 The nuclear matrix protein NMP-1 is the transcription factor YY1. Proceedings of the National Academy of Sciences of the United States of America 161 7479833
2019 The Two Sides of YY1 in Cancer: A Friend and a Foe. Frontiers in oncology 138 31824839
2018 The Yin and Yang of YY1 in tumor growth and suppression. International journal of cancer 133 29322514
2011 The oncogenic role of Yin Yang 1. Critical reviews in oncogenesis 127 22248053
2018 Transcription Factor YY1 Promotes Cell Proliferation by Directly Activating the Pentose Phosphate Pathway. Cancer research 125 29921695
2017 YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction. American journal of human genetics 125 28575647
1995 GATA1 and YY1 are developmental repressors of the human epsilon-globin gene. The EMBO journal 113 7882983
2020 The biological implications of Yin Yang 1 in the hallmarks of cancer. Theranostics 108 32226547
2019 YY1 Complex Promotes Quaking Expression via Super-Enhancer Binding during EMT of Hepatocellular Carcinoma. Cancer research 108 30760518
2023 YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6. Journal for immunotherapy of cancer 106 37094986
2014 A prominent and conserved role for YY1 in Xist transcriptional activation. Nature communications 104 25209548
2010 CXCR4/YY1 inhibition impairs VEGF network and angiogenesis during malignancy. Proceedings of the National Academy of Sciences of the United States of America 103 20660740
2017 Transcription Factor YY1 Modulates Lung Cancer Progression by Activating lncRNA-PVT1. DNA and cell biology 95 28972861
2004 YY1 DNA binding and PcG recruitment requires CtBP. Genes & development 89 15520279
2024 YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 86 38493498
1995 Cyclophilin A and FKBP12 interact with YY1 and alter its transcriptional activity. The Journal of biological chemistry 86 7541038
2016 YY1 plays an essential role at all stages of B-cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 85 27335461
2005 Inhibition of the transcription factor Yin Yang 1 activity by S-nitrosation. Biochemical and biophysical research communications 77 16143308
2007 PIASy-mediated sumoylation of Yin Yang 1 depends on their interaction but not the RING finger. Molecular and cellular biology 75 17353273
2020 CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1. Cell death & disease 73 32681092
2023 CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1. International journal of biological sciences 69 37928273
2014 Function of YY1 in Long-Distance DNA Interactions. Frontiers in immunology 66 24575094
2021 DeepYY1: a deep learning approach to identify YY1-mediated chromatin loops. Briefings in bioinformatics 65 33279983
2019 Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFβ1. Science translational medicine 63 31534017
2015 The role of YY1 in oncogenesis and its potential as a drug target in cancer therapies. Current cancer drug targets 61 25817371
2011 Mechanisms of Yin Yang 1 in oncogenesis: the importance of indirect effects. Critical reviews in oncogenesis 59 22248052
2015 YY1 suppresses FEN1 over-expression and drug resistance in breast cancer. BMC cancer 57 25885449
2013 Proviral silencing in embryonic cells is regulated by Yin Yang 1. Cell reports 57 23810560
1993 The intracisternal A-particle upstream element interacts with transcription factor YY1 to activate transcription: pleiotropic effects of YY1 on distinct DNA promoter elements. Molecular and cellular biology 57 8413258
2014 YY1 is indispensable for Lgr5+ intestinal stem cell renewal. Proceedings of the National Academy of Sciences of the United States of America 55 24821761
2013 YY1 DNA binding and interaction with YAF2 is essential for Polycomb recruitment. Nucleic acids research 54 24285299
2008 YY1's longer DNA-binding motifs. Genomics 53 18950698
2015 Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas. Proceedings of the National Academy of Sciences of the United States of America 52 25787250
2016 The adventure of delta. Liver international : official journal of the International Association for the Study of the Liver 51 26725911
2021 Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer. Nucleic acids research 44 33849067
2012 YY1 regulates melanocyte development and function by cooperating with MITF. PLoS genetics 44 22570637
2016 GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis. Cancer research 43 27312530
2014 Structure of Yin Yang 1 oligomers that cooperate with RuvBL1-RuvBL2 ATPases. The Journal of biological chemistry 43 24990942
2017 Targeting the Overexpressed YY1 in Cancer Inhibits EMT and Metastasis. Critical reviews in oncogenesis 41 29604936
2022 Homeostasis Imbalance of YY2 and YY1 Promotes Tumor Growth by Manipulating Ferroptosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 40 35246964
2014 Smurf2 regulates the degradation of YY1. Biochimica et biophysica acta 39 24803334
2001 YY1 is a positive regulator of transcription of the Col1a1 gene. The Journal of biological chemistry 38 11514536
2024 YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle. Nature genetics 35 39210046
2023 Dissecting the roles and clinical potential of YY1 in the tumor microenvironment. Frontiers in oncology 35 37081988
2021 Disruption of YY1-EZH2 Interaction Using Synthetic Peptides Inhibits Breast Cancer Development. Cancers 35 34065631
2009 YY1 is autoregulated through its own DNA-binding sites. BMC molecular biology 33 19712462
2017 The Role of Transcription Factor YY1 in the Biology of Cancer. Critical reviews in oncogenesis 32 29604933
2017 YY1 in Cell Differentiation and Tissue Development. Critical reviews in oncogenesis 32 29604941
2020 Molecular interplay between linc01134 and YY1 dictates hepatocellular carcinoma progression. Journal of experimental & clinical cancer research : CR 31 32272940
2017 A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells. Journal of translational medicine 31 29052509
2016 YY1 Is Required for Germinal Center B Cell Development. PloS one 31 27167731
2015 Epithelial inactivation of Yy1 abrogates lung branching morphogenesis. Development (Cambridge, England) 31 26329601
2021 Roles Played by YY1 in Embryonic, Adult and Cancer Stem Cells. Stem cell reviews and reports 30 33728560
2019 Functional interplay between YY1 and CARM1 promotes oral carcinogenesis. Oncotarget 30 31217904
2020 Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression. Theranostics 29 32929330
2009 YY1's role in DNA methylation of Peg3 and Xist. Nucleic acids research 29 19628663
2017 Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression. Oncogenesis 28 28394354
2017 YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress. Cancer medicine 28 28485541
2005 Transient requirements of YY1 expression for PcG transcriptional repression and phenotypic rescue. Journal of cellular biochemistry 28 16052488
2022 Long noncoding RNA LINC01435 impedes diabetic wound healing by facilitating YY1-mediated HDAC8 expression. iScience 26 35330681
2015 Regulation of Yin Yang 1 by Tyrosine Phosphorylation. The Journal of biological chemistry 26 26198631
2024 Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1. Cancers 25 38539569
2022 Dual Role of YY1 in HPV Life Cycle and Cervical Cancer Development. International journal of molecular sciences 25 35408813
2021 A missense variant in NDUFA6 confers schizophrenia risk by affecting YY1 binding and NAGA expression. Molecular psychiatry 25 33931730
2021 Multifaceted regulation of hepatic lipid metabolism by YY1. Life science alliance 25 34099540
2017 Multifunctional YY1 in Liver Diseases. Seminars in liver disease 25 29272897
2015 Critical role of YY1 in cardiac morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 23 25703143
2024 Host cells reprogram lipid droplet synthesis through YY1 to resist PRRSV infection. mBio 22 38953350
2024 Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1. Nature neuroscience 22 38956165
2023 Regulation of TREM2 expression by transcription factor YY1 and its protective effect against Alzheimer's disease. The Journal of biological chemistry 22 37044212
2018 Long noncoding RNA NPCCAT1 promotes nasopharyngeal carcinoma progression via upregulating YY1. Biochimie 22 30481541
2015 Overexpression of YY1 increases the protein production in mammalian cells. Journal of biotechnology 22 26686315
2023 SIRT1 is transcriptionally repressed by YY1 and suppresses ferroptosis in rheumatoid arthritis. Advances in rheumatology (London, England) 21 36882816
2021 Endothelial Yin Yang 1 Phosphorylation at S118 Induces Atherosclerosis Under Flow. Circulation research 21 34747636
2017 YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor. Oncotarget 21 28489564
2002 YY1 activates Msx2 gene independent of bone morphogenetic protein signaling. Nucleic acids research 21 11861914
2020 Endothelial-specific YY1 governs sprouting angiogenesis through directly interacting with RBPJ. Proceedings of the National Academy of Sciences of the United States of America 20 32075915
2019 Yy1 regulates Senp1 contributing to AMPA receptor GluR1 expression following neuronal depolarization. Journal of biomedical science 19 31629407
2018 Transcription factor YY1 is essential for iNKT cell development. Cellular & molecular immunology 19 29500401
2011 Overexpression of Yin Yang 1 in the pathogenesis of human hematopoietic malignancies. Critical reviews in oncogenesis 19 22248059
2005 Nucleophosmin/B23 regulates PCNA promoter through YY1. Biochemical and biophysical research communications 19 16099430
2023 Cross-Talks between RKIP and YY1 through a Multilevel Bioinformatics Pan-Cancer Analysis. Cancers 18 37894300
2022 miR-301a Deficiency Attenuates the Macrophage Migration and Phagocytosis through YY1/CXCR4 Pathway. Cells 18 36552718
2020 YY1-induced lncRNA DSCR8 promotes the progression of ovarian cancer via miR-3192-5p/YY1 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 32563147
2020 YY1 promotes SOCS3 expression to inhibit STAT3‑mediated neuroinflammation and neuropathic pain. Molecular medicine reports 18 33300076
2024 Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS. Proceedings of the National Academy of Sciences of the United States of America 17 38165927
2024 Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression. Cell death & disease 17 38351178
2021 YAF2-Mediated YY1-Sirtuin6 Interactions Responsible for Mitochondrial Downregulation in Aging Tunicates. Molecular and cellular biology 17 33875574
2020 LncRNA PCAT6 Regulated by YY1 Accelerates the Progression of Glioblastoma via miR-513/IGF2BP1. Neurochemical research 17 32990800
2004 CD3 delta immunodeficiency. Current opinion in allergy and clinical immunology 17 15640687
2021 Kynurenine derivative 3-HAA is an agonist ligand for transcription factor YY1. Journal of hematology & oncology 16 34563230
2018 Characterization of interaction between Trim28 and YY1 in silencing proviral DNA of Moloney murine leukemia virus. Virology 16 29407374
2017 YY1 Expression Is Sufficient for the Maintenance of Cardiac Progenitor Cell State. Stem cells (Dayton, Ohio) 15 28580685