Affinage

YY1

Transcriptional repressor protein YY1 · UniProt P25490

Length
414 aa
Mass
44.7 kDa
Annotated
2026-06-11
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YY1 is a multifunctional zinc finger transcription factor that acts as a structural organizer of the genome, binding active enhancers and promoter-proximal elements and forming dimers that establish and maintain enhancer-promoter loops in a manner analogous to CTCF (PMID:29224777). Acute degradation studies show this architectural function is required for enhancer-promoter loop maintenance but not for compartments or TADs, operates independently of cohesin-mediated loop extrusion stalling, and is cell-cycle-regulated, with YY1 partially retained on mitotic chromatin and rapidly rebinding promoters during mitotic exit (PMID:39210046). DNA recognition is achieved through concerted contributions of all four zinc fingers, with the first finger required for engaging an extended binding motif (PMID:18950698), while the N-terminal portion of the protein is an intrinsically disordered region (PMID:25963536). YY1 directs both activating and repressive transcriptional outputs depending on cofactor context: it recruits Polycomb group proteins to chromatin in a manner requiring CtBP for its DNA binding (PMID:15520279) and is bridged to PRC1 through YAF2 (PMID:24285299), and it interacts with diverse partners including c-Myc (PMID:8266081), androgen receptor (PMID:19668226), E2F1 (PMID:17980704), YAP/EZH2 (PMID:32409309), Smad7/HDAC1 (PMID:24369345), and RNA polymerase II (PMID:35113157) to tune target gene expression. YY1 directly activates or represses a broad target repertoire including c-myc (PMID:8246966), BAX (PMID:27074573), insulin genes (PMID:35113157), GLUT3 (PMID:29869834), TREM2 (PMID:37044212), PLZF (PMID:29500401), and TGFB1 (PMID:31534017), and suppresses p53 to promote cell survival (PMID:26843327). In vivo, YY1 is essential for V(H)D(H)J(H) recombination and IgH locus contraction in B cells (PMID:17504937), for endothelial development where it represses Notch signaling by competing with MAML1 for RBPJ binding (PMID:32075915), and for insulin gene expression and beta-cell mass (PMID:35113157). YY1 activity is extensively controlled by post-translational modifications: tyrosine phosphorylation at Y383 by Src-family kinases blocks DNA/RNA binding downstream of EGFR (PMID:26198631), serine phosphorylation at S118 by CK2alpha drives endothelial proliferation and atherosclerosis (PMID:34747636), SET7/9 methylation at K173/K411 modulates DNA binding (PMID:26902152) with PHF8 acting as the demethylating co-repressor at ETC genes (PMID:38165927), p300-mediated lactylation at K183 activates angiogenic transcription (PMID:37085894), and protein stability is set by the opposing actions of the Smurf2 E3 ligase (PMID:24803334) and the OTUD3 deubiquitinase (PMID:38351178). Beyond transcription, YY1 directly binds AKT to promote mTORC2-mediated AKT-S473 phosphorylation independently of its transcriptional activity (PMID:26762111) and modulates antiviral interferon signaling through interaction with STAT1 (PMID:29161701).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1993 High

    Established YY1 as a sequence-specific transcriptional activator with defined endogenous targets and identified c-Myc as a direct interacting negative regulator, defining YY1 as a context-dependent transcription factor rather than a simple activator or repressor.

    Evidence Protein purification, recombinant binding and reporter assays at the c-myc promoter, plus yeast two-hybrid and affinity chromatography for the c-Myc interaction

    PMID:8246966 PMID:8266081

    Open questions at the time
    • Did not establish how cofactor context switches YY1 between activation and repression
    • Mechanism of c-Myc inhibition of YY1 not resolved at the structural level
  2. 2001 Medium

    Showed that YY1 transactivation requires domains beyond the zinc fingers, demonstrating that DNA binding and activation are separable functions.

    Evidence Yeast one-hybrid, EMSA/supershift, and reporter assays with a zinc-finger-only truncation at the PLP promoter in oligodendrocyte lines

    PMID:11331422

    Open questions at the time
    • Specific transactivation domain not mapped
    • Single cell-type context
  3. 2004 High

    Revealed that YY1 recruits Polycomb group proteins and directs repressive histone modifications, and that CtBP is required for YY1 DNA binding in vivo, linking YY1 to Polycomb silencing.

    Evidence Drosophila genetic epistasis in CtBP mutants with ChIP and histone modification readouts

    PMID:15520279

    Open questions at the time
    • Molecular basis of CtBP control over DNA binding unresolved
    • Conservation of CtBP requirement in mammals not addressed here
  4. 2007 High

    Demonstrated a direct in vivo requirement for YY1 in long-range DNA interactions controlling antigen receptor diversification, providing early evidence for an architectural function.

    Evidence Conditional B-cell knockout with 3D DNA FISH, ChIP at the Emu enhancer, and IgH transgene rescue

    PMID:17504937

    Open questions at the time
    • Did not distinguish architectural from purely transcriptional roles at the IgH locus
    • Looping partner proteins not defined
  5. 2008 Medium

    Defined the DNA-recognition logic of YY1, showing all four zinc fingers contribute and the first finger enables binding to an extended motif.

    Evidence EMSA and zinc-finger mutagenesis on consensus and extended motifs in vitro

    PMID:18950698

    Open questions at the time
    • No co-crystal structure
    • Genomic relevance of extended motif not tested in cells
  6. 2013 High

    Identified YAF2 as the bridge connecting YY1 DNA binding to PRC1, establishing a molecular route for YY1-directed Polycomb assembly.

    Evidence Reciprocal Co-IP, ChIP, and cross-species genetic rescue with siRNA knockdown in HeLa cells

    PMID:24285299

    Open questions at the time
    • Stoichiometry of YY1-YAF2-PRC1 complex not defined
    • Genome-wide scope of YY1/YAF2 Polycomb targets not mapped
  7. 2014 High

    Characterized YY1 self-association into a bell-shaped dimer/oligomer and linked it to homologous recombination via RuvBL1-RuvBL2, revealing a non-canonical DNA-repair function.

    Evidence Electron microscopy, bimolecular fluorescence complementation, in vitro DNA binding, pulldowns, and RAD51 foci assays

    PMID:24990942

    Open questions at the time
    • Relationship of oligomerization to enhancer-promoter looping not directly tested
    • Physiological setting of HR function unclear
  8. 2016 High

    Resolved the YY1-p53 regulatory axis through clean genetic epistasis, showing YY1 promotes survival by suppressing p53.

    Evidence Stage-specific conditional KO and YY1/p53 double KO rescue in thymocytes with apoptosis assays

    PMID:26843327

    Open questions at the time
    • Direct mechanism of p53 suppression by YY1 in thymocytes not detailed
    • Whether suppression is transcriptional or post-translational not resolved here
  9. 2016 Medium

    Uncovered a transcription-independent role for YY1 as a direct AKT-binding scaffold promoting mTORC2-mediated AKT-S473 phosphorylation, expanding YY1 beyond the nucleus.

    Evidence Co-IP, OPB-domain mapping (G201-S226), peptide competition, PI3K inhibition, and proliferation assays

    PMID:26762111

    Open questions at the time
    • Subcellular site of YY1-AKT interaction not defined
    • Structural basis of OPB-AKT contact unknown
  10. 2016 Medium

    Established SET7/9 methylation of YY1 at K173/K411 as a direct regulator of its DNA-binding and transcriptional activity, opening the PTM dimension of YY1 control.

    Evidence In vitro methyltransferase assay, mutagenesis, ChIP, reporter and proliferation assays

    PMID:26902152

    Open questions at the time
    • Genome-wide consequences of methylation not mapped
    • Reader of methylated YY1 not identified at the time
  11. 2015 High

    Defined tyrosine phosphorylation of YY1 at Y383 by Src-family kinases as a switch that blocks DNA/RNA binding downstream of EGFR, linking growth-factor signaling to YY1 inactivation.

    Evidence Kinase inhibition, overexpression and knockout, Y383 mutagenesis, and DNA/RNA binding and reporter assays

    PMID:26198631

    Open questions at the time
    • In vivo physiological contexts of Y383 phosphorylation not defined
    • Phosphatase reversing the mark not identified
  12. 2014 Medium

    Identified Smurf2 as an E3 ligase that polyubiquitinates YY1 via a PPxY motif to control its half-life, defining the degradative arm of YY1 regulation.

    Evidence Co-IP, ubiquitination and cycloheximide-chase assays, PPxY mutant analysis, and reporter assays

    PMID:24803334

    Open questions at the time
    • In vivo relevance of Smurf2-YY1 axis not established
    • Signals triggering YY1 degradation unknown
  13. 2017 High

    Defined YY1 as a genome-wide structural regulator of enhancer-promoter looping analogous to CTCF, the central architectural model for the protein.

    Evidence ChIP-seq, HiChIP, CRISPR binding-site deletion, auxin-inducible degron depletion, and chromosome conformation capture

    PMID:29224777

    Open questions at the time
    • Did not resolve relationship to cohesin/loop extrusion
    • Cell-cycle dynamics of looping not addressed
  14. 2024 High

    Showed YY1-dependent looping is cohesin-extrusion-independent and cell-cycle-coupled, with mitotic bookmarking and rapid rebinding at mitotic exit refining the architectural model.

    Evidence Acute auxin-degron degradation with Hi-C, ChIP-seq, and mitosis-to-G1 synchronization in erythroid cells

    PMID:39210046

    Open questions at the time
    • Mechanism distinguishing YY1 loops from CTCF/cohesin loops molecularly unresolved
    • How mitotic retention is established not defined
  15. 2020 High

    Established an essential in vivo developmental role for YY1 in endothelium and a precise mechanism: repression of Notch by competing with MAML1 for RBPJ binding.

    Evidence Endothelial-specific conditional KO with retinal angiogenesis, Co-IP, domain mapping, and Notch target analysis

    PMID:32075915

    Open questions at the time
    • Whether this competition operates outside endothelium not addressed
    • Effect on YY1 architectural function during vascular development not tested
  16. 2021 High

    Linked CK2alpha-mediated S118 phosphorylation of YY1 to endothelial proliferation and atherosclerosis through a phospho-YY1/ZKSCAN4/HDM2/p53-p21 pathway, providing in vivo PTM-to-disease causality.

    Evidence Phosphoproteomics, yeast two-hybrid, proximity ligation, Co-IP, and EC-specific S118A transgenic mice in an ApoE-KO atherosclerosis model

    PMID:34747636

    Open questions at the time
    • Interplay between S118 phosphorylation and architectural function unknown
    • Relevance to other vascular beds not tested
  17. 2023 High

    Identified p300-mediated lactylation of YY1 (at K183) as an activating PTM coupling metabolic state to angiogenic and inflammatory gene transcription.

    Evidence Mass spectrometry site mapping, K183 mutagenesis, ChIP/CUT&Tag, reporter assays, and p300 inhibition in vivo and in vitro

    PMID:37085894 PMID:38493498

    Open questions at the time
    • Eraser of YY1 lactylation not identified
    • Microglial lactylation site(s) not mapped
  18. 2024 Medium

    Completed a methylation read-write-erase axis by identifying PHF8 as the YY1 demethylase acting as a co-repressor at ETC genes to drive mitochondrial ROS and tumor growth.

    Evidence PHF8 KO/inhibition, YY1 methylation assays, ETC gene profiling, mROS measurement, and PDX xenografts

    PMID:38165927

    Open questions at the time
    • Direct demethylation of specific YY1 residues by PHF8 not fully resolved
    • Single-lab finding
  19. 2024 Medium

    Identified OTUD3 as a stabilizing deubiquitinase for YY1 regulated by PLK1 phosphorylation, defining the counterbalance to Smurf2-mediated turnover.

    Evidence DUB screen, Co-IP, ubiquitination and cycloheximide-chase assays, and PLK1 phospho-mutant analysis in CRC cells

    PMID:38351178

    Open questions at the time
    • In vivo relevance of OTUD3-YY1 axis not established
    • Crosstalk with Smurf2 not directly tested
  20. 2024 High

    Demonstrated YY1 acts as a required cofactor downstream of a master transcription factor (Ngn2), activating neuronal enhancers and remodeling 3D architecture during cell-fate reprogramming.

    Evidence Single-cell multiomics, ChIP-seq, 3D architecture and DNA methylation profiling, conditional Yy1 deletion, and Ngn2 Co-IP

    PMID:38956165

    Open questions at the time
    • Generality of the Ngn2-YY1 cofactor relationship to other lineage factors unknown
    • Whether YY1 looping function is the operative mechanism not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how YY1's many post-translational modifications, oligomerization state, and diverse cofactor interactions are integrated to switch between its architectural looping function and its locus-specific activating versus repressive transcriptional outputs.
  • No unified model linking PTM status to choice of architectural vs transcriptional mode
  • Structural basis of YY1 dimer/oligomer at loops not defined
  • Determinants of activator-versus-repressor cofactor selection at individual loci unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 6 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4
Partners
AKTC-MYCCTBPRBPJRUVBL1SMAD7STAT1YAF2
Complex memberships
PRC1 (via YAF2)

Evidence

Reading pass · 44 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 enhancer-promoter looping. 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 interactions analogous to CTCF. ChIP-seq, HiChIP, CRISPR deletion of binding sites, auxin-inducible degron protein depletion, chromosome conformation capture Cell High 29224777
2024 Acute degradation of YY1 in erythroid cells revealed its requirement for maintenance of enhancer-promoter loops but not compartments or TADs. YY1-dependent enhancer-promoter loop formation does not involve stalling of cohesin-mediated loop extrusion. YY1 is partially retained on mitotic chromatin at gene promoters and rapidly rebinds during mitotic exit coinciding with enhancer-promoter loop establishment; cell cycle stage influences YY1's architectural function. Auxin-inducible degron acute degradation, Hi-C, ChIP-seq, mitosis-to-G1 cell synchronization Nature genetics High 39210046
1993 YY1 physically associates with c-Myc (but not Max), and c-Myc inhibits both the repressor and activator functions of YY1 in cotransfection experiments, establishing c-Myc as a negative regulator of YY1 transcriptional activity. Yeast two-hybrid screen, affinity chromatography, cotransfection reporter assays Science Medium 8266081
1993 YY1 (identified as CF1) directly binds two sites in the murine c-myc promoter (-260 and -390 bp from P1) and strongly activates c-myc transcription; overexpression of YY1 in erythroleukemia cells increases endogenous c-myc mRNA from both major initiation sites. Protein purification, immunological cross-reactivity, recombinant protein binding assays, cotransfection reporter assays, Northern blotting Molecular and cellular biology High 8246966
2023 YY1 is lactylated at lysine 183 (K183) by the acetyltransferase p300; hyperlactylated YY1 directly enhances FGF2 transcription and promotes angiogenesis. YY1 K183 mutation eliminates these effects, and p300 overexpression increases YY1 lactylation and angiogenesis. Mass spectrometry identification of lactylation sites, site-directed mutagenesis (K183), ChIP, luciferase reporter assays, p300 inhibitor A485 in vivo/in vitro Genome biology High 37085894
2024 YY1 is lactylated at an unspecified site(s) by p300 in microglia; this lactylation promotes microglial activation by upregulating transcription of inflammatory genes including STAT3, CCL5, IRF1, IDO1, and SEMA4D. Inhibition of p300 decreases YY1 lactylation and suppresses microglial inflammation. CUT&Tag analysis, p300 inhibitor treatment, in vivo/in vitro inflammation assays Advanced science Medium 38493498
2007 Conditional ablation of YY1 in mouse B cells caused a defect in somatic V(H)D(H)J(H) rearrangement, a block in pro-B to pre-B cell transition, and impaired IgH locus contraction. YY1 binds the intronic Eµ enhancer within the IgH locus, indicating a direct role in controlling long-distance DNA interactions required for V(H)D(H)J(H) recombination. Conditional knockout (Cre-loxP), 3D DNA FISH, ChIP, B-cell development assays, IgH transgene rescue Genes & development High 17504937
2004 In Drosophila, YY1 can recruit Polycomb group (PcG) proteins to Polycomb response elements, leading to deacetylation and methylation of histone H3. This PcG recruitment and concomitant histone modification require CtBP; in a CtBP mutant background, YY1 DNA binding in vivo is also ablated without YY1 degradation or nuclear export, suggesting CtBP controls YY1 DNA-binding ability. In vivo Drosophila genetics (CtBP mutant), ChIP, histone modification assays, immunostaining Genes & development High 15520279
2013 YY1 physically interacts with YAF2, which bridges YY1 to the PRC1 complex. YAF2 is responsible for PcG recruitment to DNA mediated by YY1 DNA binding; knockdown of YY1 abolishes PcG recruitment and is not compensated by exogenous YAF2, demonstrating YY1 DNA binding is required for Polycomb chromatin assembly. Biochemical pulldown, Co-IP, ChIP assays in HeLa cells, Drosophila complementation genetics, siRNA knockdown Nucleic acids research High 24285299
2014 YY1 assembles into homo-oligomeric species built from a bell-shaped dimer, characterized by electron microscopy. YY1 self-association occurs in vivo (bimolecular fluorescence complementation). YY1 oligomers bind DNA substrates lacking the consensus YY1 sequence in vitro, and DNA binding is enhanced by RuvBL1-RuvBL2 ATPases. YY1 oligomers bind RuvBL1-RuvBL2, preferentially interacting with RuvBL1. YY1 and the ATPase activity of RuvBL2 are required for RAD51 foci formation during homologous recombination. Electron microscopy, bimolecular fluorescence complementation, in vitro DNA binding assays, Co-IP/pulldown, RAD51 foci assay The Journal of biological chemistry High 24990942
2016 SET7/9 (KMT7) methylates YY1 at K173 and K411; this methylation regulates YY1 DNA-binding activity both in vitro and at specific genomic loci in cells, and affects YY1-regulated gene transcription and cell proliferation. In vitro methyltransferase assay, site-directed mutagenesis, ChIP, reporter assays, cell proliferation assays Scientific reports Medium 26902152
2015 YY1 is tyrosine-phosphorylated by multiple Src family kinases in vitro and in vivo. Phosphorylation at tyrosine 383 interferes with DNA and RNA binding, leading to downregulation of YY1 transcriptional activity. YY1 is also a downstream target of EGFR signaling in vivo. Pharmacological kinase inhibition, kinase overexpression, kinase knockout, site-directed mutagenesis (Y383), DNA/RNA binding assays, reporter assays The Journal of biological chemistry High 26198631
2014 Smurf2 E3 ubiquitin ligase physically interacts with YY1 via a PPxY motif on YY1, induces poly-ubiquitination of YY1, and shortens YY1 protein half-life via the ubiquitin-proteasome pathway. Smurf2 reduces YY1-mediated transcriptional activation and relieves YY1-mediated suppression of p53 activity. Co-IP, ubiquitination assay, half-life assay (cycloheximide chase), PPxY mutant analysis, reporter assays, siRNA knockdown Biochimica et biophysica acta Medium 24803334
2016 YY1 promotes AKT phosphorylation at S473 through direct physical interaction with AKT; the AKT-binding site maps to residues G201-S226 (designated the OPB domain) on YY1. YY1-promoted AKT phosphorylation is mediated through mTORC2, is independent of PI3K activity and YY1 transcriptional activity. A peptide based on the OPB domain blocks YY1-AKT interaction and reduces AKT phosphorylation and cell proliferation. Co-IP, domain mapping, mTORC2 interaction assays, pharmacological PI3K inhibition, peptide competition, cell proliferation assays, tissue microarray Journal of molecular cell biology Medium 26762111
2009 YY1 physically interacts with androgen receptor (AR) both in cell-free systems and in cultured cells. YY1 is required for optimal AR transcriptional activity at the PSA promoter and is a necessary component of the complex binding the androgen response element. YY1 depletion reduces endogenous PSA levels in LNCaP cells. Co-IP, cell-free binding assay, ChIP, luciferase reporter assay, siRNA knockdown Oncogene Medium 19668226
2020 YAP interacts with YY1 and EZH2 to function as a transcriptional repressor. YAP colocalization with YY1 and EZH2 on the genome represses genes including the cell-cycle inhibitor p27, contributing to loss of contact inhibition. Genome-wide ChIP-seq, Co-IP, transcriptome profiling, loss-of-function experiments Cancer research Medium 32409309
2020 Endothelial cell-specific YY1 deletion causes embryonic lethality due to vascular defects. YY1 functions as a repressor of Notch signaling by binding to the N-terminal domain of RBPJ and competing with MAML1 for RBPJ binding, thereby impairing NICD/MAML1/RBPJ complex formation and Notch target gene expression to control endothelial tip-stalk fate determination. Conditional endothelial-specific KO (Cre-loxP), retinal sprouting angiogenesis assay, Co-IP, domain-mapping binding assays, Notch target gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 32075915
2021 Disturbed flow induces phosphorylation of YY1 at serine 118 (phospho-YY1-S118) in endothelial cells via direct interaction with CK2α (casein kinase 2α). Phospho-YY1-S118 directly binds ZKSCAN4, inducing HDM2 promoter activity and gene expression, which promotes EC proliferation through downregulation of p53 and p21. EC-specific expression of a S118-nonphosphorylatable YY1 mutant in ApoE-deficient mice reduces atherosclerosis formation. Phosphoproteomics, yeast 2-hybrid screening, in situ proximity ligation, Co-IP, transgenic mouse model (EC-specific S118A mutant), ApoE-KO atherosclerosis model, CK2 inhibitor treatment Circulation research High 34747636
2013 YY1 interacts with Smad7, and this interaction is attenuated by TGF-β signaling. YY1 and Smad7 act in concert to inhibit TGF-β-induced transcription in the nucleus. Smad7 enhances YY1's interaction with HDAC1, and YY1 and HDAC1 augment the transcriptional repression activity of Smad7. Co-IP, reporter assays, target gene expression analysis, Gal4-luciferase reporter Science China. Life sciences Medium 24369345
2019 YY1 binds the TGFB1 promoter and represses TGFB1 transcription in human renal mesangial cells. In mouse models, YY1 overexpression attenuates glomerulosclerosis and YY1 knockdown aggravates it, establishing YY1 as a potent transcriptional repressor of TGFB1. Mass spectrometry-based DNA-protein interaction screen, ChIP, luciferase reporter, siRNA knockdown/adenoviral overexpression in mouse models Science translational medicine High 31534017
2008 YY1 recognizes longer DNA-binding motifs (GGCGCCATnTT and CCGCCATnTT) beyond the known consensus (CGCCATnTT). Gel shift assays demonstrate higher affinity for the longer motif. Substitutions in the first zinc finger unit weaken DNA-binding specificity at both 5'- and 3'-flanks of the longer motif, indicating the first zinc finger is required for recognition of the extended motif and that DNA recognition involves concerted contribution of all four zinc finger units. Gel shift assays (EMSA), in vitro DNA-binding motif studies, zinc finger mutagenesis Genomics Medium 18950698
2015 YY1 is a transcriptional repressor of FEN1; YY1 binds the FEN1 promoter and suppresses FEN1 expression. In response to chemotherapeutic drugs (MMC, Taxol), YY1 is dissociated from the FEN1 promoter, leading to FEN1 overexpression. Overexpression of YY1 in cancer cells downregulates FEN1 and sensitizes cells to these drugs. ChIP, luciferase reporter assay, siRNA knockdown/overexpression, drug sensitivity assays BMC cancer Medium 25885449
2019 YY1 regulates Bmp7 and Ctgf reporter activities and modulates their gene expression in cardiomyocytes. Upregulation of YY1 suppresses LMNA-deficiency-induced dilated cardiomyopathy and cardiac fibrosis by inducing Bmp7 expression and preventing upregulation of Ctgf, which in turn downregulates TGF-β/Smad signaling. shRNA-induced Lmna DCM mouse model, adenoviral YY1 overexpression, Bmp7 knockdown, Ctgf silencing, reporter assays, gene expression analysis Circulation research Medium 31495264
2010 TGF-β induces YY1 expression in lung fibroblasts via NF-κB (blocked by IκB degradation inhibitor). YY1 upregulates α-SMA expression in pulmonary fibroblasts. YY1-deficient (YY1+/-) mice are significantly protected from lung fibrosis with attenuated α-SMA and collagen expression; conditional YY1 deletion via adenovirus-Cre reduced lung fibrosis in floxed mice. Conditional knockout mice (Cre-loxP, partial heterozygous), NF-κB inhibition, α-SMA promoter reporter, siRNA knockdown, bleomycin/silica fibrosis models American journal of respiratory and critical care medicine Medium 21169469
2012 YY1 promotes hepatic gluconeogenesis by transcriptionally upregulating glucocorticoid receptor (GR) expression. Liver-specific ablation of YY1 via adenoviral shRNA ameliorates hyperglycemia in wild-type and diabetic db/db mice; YY1 overexpression in liver augments gluconeogenesis and raises fasting blood glucose. Adenoviral shRNA knockdown, adenoviral overexpression, liver-specific genetic manipulation, blood glucose measurement, gene expression analysis Diabetes Medium 23193188
2009 YY1 knockdown during oogenesis results in loss of DNA methylation on Peg3 and Xist DMRs but not Nespas or H19. Continued YY1 knockdown from oogenesis to blastocyst causes further loss of DNA methylation on Peg3, and high incidence of embryonic lethality follows, indicating YY1 plays a role in de novo DNA methylation of these imprinted loci during oogenesis. Conditional YY1 knockdown (stage-specific), bisulfite sequencing of DMRs, embryo phenotyping Nucleic acids research Medium 19628663
2016 YY1 promotes thymocyte survival by suppressing p53 expression; YY1-deficient thymocytes show increased apoptosis and developmental block, which is completely rescued by concurrent loss of p53, placing YY1 upstream of p53 in thymocyte survival pathway. Conditional KO (Cre-loxP at two developmental stages), double KO (YY1/p53), flow cytometry, apoptosis assays Journal of immunology High 26843327
2018 YY1 directly binds the PLZF gene promoter (shown by ChIP-seq) and activates PLZF transcription; YY1-deficient thymocytes undergo normal Vα14-Jα18 rearrangements but display impaired survival and fail to develop iNKT cells due to absent PLZF induction. Conditional KO (Cre-loxP), ChIP-seq, deep sequencing of Vα14-Jα18 rearrangements, flow cytometry, apoptosis assays Cellular & molecular immunology High 29500401
2007 YY1 and E2F1 physically interact in the nucleus and synergistically activate p73 promoter activity. Both factors are required for doxorubicin-induced p73 promoter activation; YY1 silencing reduces endogenous p73 expression, while YY1 overexpression induces p73 promoter activity. Co-IP, immunofluorescence, luciferase reporter assay, siRNA knockdown, doxorubicin treatment Biochemical and biophysical research communications Medium 17980704
2016 YY1 directly binds the BAX promoter (shown by luciferase reporter, EMSA, and ChIP assays) and transcriptionally activates Bax, promoting its mitochondrial localization, cytochrome c release, and caspase activation in pancreatic cancer cells. Luciferase reporter assay, EMSA, ChIP, Western blotting, mitochondrial fractionation, caspase activation assay Oncotarget Medium 27074573
2022 In pancreatic β-cells, YY1 directly binds enhancer regions in exon 2 of Ins1 and Ins2 genes and activates insulin transcription. YY1 also directly interacts with RNA polymerase II, potentially stabilizing enhancer-promoter interactions during transcription initiation. β-cell-specific Yy1 ablation causes rapid-onset hyperglycemia and reduced β-cell mass. Conditional KO, ChIP assays (YY1, H3K4me1, H3K27ac, H3K27me3), RNA-seq, luciferase reporter assays, Co-IP (YY1-Pol II) Diabetes High 35113157
2001 YY1 binds to the myelin PLP promoter in vitro and in vivo (via yeast one-hybrid and gel shift/supershift with YY1 antibody). Overexpression of YY1 in oligodendrocyte cell lines enhances PLP promoter transcription; a truncated YY1 containing only the four zinc finger domains has little effect, indicating the non-zinc-finger domains are required for transactivation. Yeast one-hybrid, gel shift assay, antibody supershift, cotransfection reporter assay, promoter mutation analysis Journal of neurochemistry Medium 11331422
2014 YY1 regulates SQSTM1 expression through epigenetic modulation of MIR372 transcription; YY1 suppresses MIR372 expression during nutrient starvation, leading to increased SQSTM1 (p62) and autophagy flux activation. YY1 knockdown inhibits cell viability and autophagy flux through SQSTM1 downregulation. siRNA knockdown, miRNA overexpression, luciferase reporter assay, autophagy flux assays (LC3-II, electron microscopy), in vivo tumor growth Autophagy Medium 24991827
2017 YY1 activates GLUT3 transcription by directly binding to its promoter, enhancing tumor cell aerobic glycolysis in a p53-independent manner. This regulation is critical for YY1-induced tumor cell proliferation and tumorigenesis. Oxaliplatin suppresses colon carcinoma cell proliferation by inhibiting the YY1/GLUT3 axis. ChIP, luciferase reporter assay, siRNA knockdown/overexpression, glycolysis assays, cell proliferation assays Cancer science Medium 29869834
2024 PHF8 demethylates YY1 (at methylation sites established by SET7/9), functioning as a co-repressor with YY1 for nuclear-encoded ETC genes, driving mitochondrial ROS production and cancer cell growth. PHF8 pharmacological inhibition (iPHF8) regulates YY1 methylation, ETC gene transcription, mROS production, and suppresses tumor growth in xenograft models. PHF8 knockout/inhibition, YY1 methylation assays, ETC gene expression profiling, mROS measurement, cell-line and PDX xenograft models Proceedings of the National Academy of Sciences of the United States of America Medium 38165927
2024 OTUD3 deubiquitinase physically interacts with YY1, inhibits its ubiquitin-proteasome-mediated degradation, and increases YY1 protein levels. PLK1 phosphorylates OTUD3 at S326, enhancing OTUD3 binding to and deubiquitination of YY1. DUB screen, Co-IP, ubiquitination assay, cycloheximide chase, PLK1 kinase assay, phospho-mutant analysis, CRC cell proliferation assays Cell death & disease Medium 38351178
2019 In un-stimulated neurons, a YY1-Brd4 transcription factor complex assembled at the Senp1 promoter activates Senp1 transcription. Upon neuronal membrane depolarization, YY1 is dephosphorylated and the YY1-Brd4 complex is evicted from the Senp1 promoter, reducing Senp1 transcription and subsequently decreasing GluR1 expression. Co-IP, ChIP, in vitro DNA binding assay, luciferase reporter assay, siRNA knockdown, phosphatase inhibitor experiments, qRT-PCR/Western blot Journal of biomedical science Medium 31629407
2024 YY1 is recruited by direct interaction with Neurogenin2 (Ngn2) to Ngn2 target sites during astrocyte-to-neuron reprogramming. Upon Yy1 deletion, activation of neuronal enhancers and genes and reprogramming efficiency are impaired without affecting Ngn2 binding, indicating YY1 acts as a required cofactor downstream of Ngn2 binding. Single-cell multiomics, ChIP-seq, genome-wide 3D nuclear architecture profiling, DNA methylation profiling, conditional Yy1 deletion, Ngn2 Co-IP Nature neuroscience High 38956165
2022 YY1 depletion in extended pluripotent stem cells (EPSCs) triggers changes in DNA methylation, histone modifications, and high-order chromatin structures including disruption of enhancer-promoter interactions for EPSC-specific genes. YY1 loss results in DNA hypomethylation and reduced H3K4me3 and H3K27ac at EPSC-specific gene promoters (including Dnmt3l) by upregulating Kdm5c and Hdac6 through facilitation of CTCF-mediated EP interactions at their loci. siRNA knockdown, ChIP-seq (multiple histone marks), ATAC-seq, Hi-C, WGBS, scRNA-seq, luciferase reporter Nucleic acids research Medium 35425987
2017 YY1 interacts with STAT1 in the absence of viral infection. Following viral infection, YY1 protein expression decreases. YY1 knockdown reduces phosphorylated TBK1 and pIRF3 (impairing IFN-β production), while YY1 overexpression upregulates pTBK1 and pIRF3 and promotes IFN-β induction. YY1 knockdown upregulates pSTAT1/pSTAT2 and antiviral ISGs and inhibits viral replication. Co-IP, siRNA knockdown, overexpression, immunoblotting, real-time PCR Cellular physiology and biochemistry Medium 29161701
2023 YY1 directly binds the minimal promoter of TREM2 and activates its transcription in microglial cells; YY1 silencing reduces TREM2 promoter activity and protein levels in BV2 and Neuro2A cells. Luciferase assay, DNA pull-down, EMSA, shRNA knockdown The Journal of biological chemistry Medium 37044212
2023 YY1 forms a phase-separated complex (LLPS) in M2 macrophages with p300, p65, and CEBPB as transcriptional cofactors; this complex upregulates IL-6 by promoting IL-6 enhancer-promoter interactions revealed by H3K27ac ChIP-seq and YY1 ChIP-seq. LLPS assay, H3K27ac ChIP-seq, YY1 ChIP-seq, CRISPR-Cas9 KO, RNA-seq, Co-IP Journal for immunotherapy of cancer Medium 37094986
2015 YY1 N-terminal domain is an intrinsically disordered region with little residual secondary structure and no defined tertiary structure, as characterized by fluorescence, circular dichroism, gel filtration, and proteolytic susceptibility assays. The full-length YY1 protein belongs to the family of intrinsically disordered proteins. Fluorescence spectroscopy, circular dichroism, gel filtration chromatography, proteolytic susceptibility, bioinformatics Proteins Medium 25963536
2019 YY1 directly regulates Bmp7 and Ctgf promoter/reporter activities in cardiomyocytes; overexpression of YY1 maintains H3K9Ac, H3K27Ac, and H3K4Me3 at the Nkx2-5 cardiac enhancer along with enrichment of Pol II, p300, and Brg1, thereby maintaining cardiac progenitor cell state and preventing cardiomyogenic differentiation. ChIP (multiple histone marks), luciferase reporter assay, YY1 overexpression in cardiac progenitor cells, genome-wide transcriptional profiling Stem cells Medium 28580685

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 783 29224777
2006 Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene 639 16314846
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 252 37085894
2007 Yin Yang 1 is a critical regulator of B-cell development. Genes & development 215 17504937
1993 Yin-yang 1 activates the c-myc promoter. Molecular and cellular biology 173 8246966
2020 The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1. Frontiers in cell and developmental biology 161 33102493
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 128 22248053
1995 GATA1 and YY1 are developmental repressors of the human epsilon-globin gene. The EMBO journal 113 7882983
2023 YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6. Journal for immunotherapy of cancer 111 37094986
2010 Yin Yang 1: a multifaceted protein beyond a transcription factor. Transcription 110 21326896
2020 The biological implications of Yin Yang 1 in the hallmarks of cancer. Theranostics 108 32226547
2008 The Yin and Yang of YY1 in the nervous system. Journal of neurochemistry 108 18485096
2024 YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 97 38493498
2004 YY1 DNA binding and PcG recruitment requires CtBP. Genes & development 90 15520279
2010 Yin yang 1 expression in human tumors. Cell cycle (Georgetown, Tex.) 75 20081375
2023 CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1. International journal of biological sciences 74 37928273
2009 Yin Yang 1 regulates the transcriptional activity of androgen receptor. Oncogene 71 19668226
2020 YAP-Mediated Recruitment of YY1 and EZH2 Represses Transcription of Key Cell-Cycle Regulators. Cancer research 68 32409309
2011 Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation. Oncogene 68 21666725
2019 Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFβ1. Science translational medicine 67 31534017
2014 Function of YY1 in Long-Distance DNA Interactions. Frontiers in immunology 67 24575094
2015 The role of YY1 in oncogenesis and its potential as a drug target in cancer therapies. Current cancer drug targets 61 25817371
2014 Yin Yang 1 is a target of microRNA-34 family and contributes to gastric carcinogenesis. Oncotarget 61 24970812
2014 YY1-MIR372-SQSTM1 regulatory axis in autophagy. Autophagy 61 24991827
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 YY1 DNA binding and interaction with YAF2 is essential for Polycomb recruitment. Nucleic acids research 54 24285299
2009 Yin yang 1 modulates taxane response in epithelial ovarian cancer. Molecular cancer research : MCR 54 19208743
2008 YY1's longer DNA-binding motifs. Genomics 54 18950698
2019 Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of Bmp7 and Ctgf. Circulation research 52 31495264
2010 Yin yang 1 is a novel regulator of pulmonary fibrosis. American journal of respiratory and critical care medicine 51 21169469
2018 Yin Yang 1 promotes the Warburg effect and tumorigenesis via glucose transporter GLUT3. Cancer science 47 29869834
2016 Regulation of Transcription Factor Yin Yang 1 by SET7/9-mediated Lysine Methylation. Scientific reports 44 26902152
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 42 29604936
2019 Yin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner. Nature communications 41 31097699
2011 Yin Yang 1 in human cancer. Critical reviews in oncogenesis 41 22248058
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
2024 YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle. Nature genetics 38 39210046
2022 YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency. Nucleic acids research 36 35425987
2017 YY1 Is an Inducer of Cancer Metastasis. Critical reviews in oncogenesis 36 29604932
2023 Dissecting the roles and clinical potential of YY1 in the tumor microenvironment. Frontiers in oncology 35 37081988
2016 Yin Yang 1 promotes mTORC2-mediated AKT phosphorylation. Journal of molecular cell biology 35 26762111
2012 Yin Yang 1 promotes hepatic gluconeogenesis through upregulation of glucocorticoid receptor. Diabetes 35 23193188
2016 Yin Yang-1 increases apoptosis through Bax activation in pancreatic cancer cells. Oncotarget 33 27074573
2001 The transcriptional regulator Yin Yang 1 activates the myelin PLP gene. Journal of neurochemistry 33 11331422
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
2016 YY1 Is Required for Germinal Center B Cell Development. PloS one 32 27167731
1993 Characterization of the mouse gene that encodes the delta/YY1/NF-E1/UCRBP transcription factor. Proceedings of the National Academy of Sciences of the United States of America 32 8516301
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
2021 Roles Played by YY1 in Embryonic, Adult and Cancer Stem Cells. Stem cell reviews and reports 30 33728560
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
2016 Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53. Journal of immunology (Baltimore, Md. : 1950) 28 26843327
2024 Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1. Cancers 27 38539569
2018 Multiple roles of Ring 1 and YY1 binding protein in physiology and disease. Journal of cellular and molecular medicine 26 29383875
2015 Regulation of Yin Yang 1 by Tyrosine Phosphorylation. The Journal of biological chemistry 26 26198631
2007 Yin Yang 1 induces transcriptional activity of p73 through cooperation with E2F1. Biochemical and biophysical research communications 26 17980704
2022 Dual Role of YY1 in HPV Life Cycle and Cervical Cancer Development. International journal of molecular sciences 25 35408813
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
2024 Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1. Nature neuroscience 24 38956165
2022 YY1 Regulates Glucose Homeostasis Through Controlling Insulin Transcription in Pancreatic β-Cells. Diabetes 24 35113157
2022 YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance. Frontiers in oncology 24 35719931
2024 Host cells reprogram lipid droplet synthesis through YY1 to resist PRRSV infection. mBio 23 38953350
2023 Regulation of TREM2 expression by transcription factor YY1 and its protective effect against Alzheimer's disease. The Journal of biological chemistry 23 37044212
2017 Yin Yang 1 (YY1): Regulation of Survivin and Its Role In Invasion and Metastasis. Critical reviews in oncogenesis 23 29604934
2022 YY1 (Yin-Yang 1), a transcription factor regulating systemic inflammation, is involved in cognitive impairment of depression. Psychiatry and clinical neurosciences 22 36436207
2021 Endothelial Yin Yang 1 Phosphorylation at S118 Induces Atherosclerosis Under Flow. Circulation research 22 34747636
2017 Yin Yang 1 Dynamically Regulates Antiviral Innate Immune Responses During Viral Infection. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 22 29161701
2015 Intrinsic disorder of human Yin Yang 1 protein. Proteins 22 25963536
2023 SIRT1 is transcriptionally repressed by YY1 and suppresses ferroptosis in rheumatoid arthritis. Advances in rheumatology (London, England) 21 36882816
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 21 32075915
2017 YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor. Oncotarget 21 28489564
2017 Therapeutic YY1 Inhibitors in Cancer: ALL in ONE. Critical reviews in oncogenesis 21 29604935
2023 Cross-Talks between RKIP and YY1 through a Multilevel Bioinformatics Pan-Cancer Analysis. Cancers 19 37894300
2022 miR-301a Deficiency Attenuates the Macrophage Migration and Phagocytosis through YY1/CXCR4 Pathway. Cells 19 36552718
2020 Yin Yang 1 is critical for mid-hindbrain neuroepithelium development and involved in cerebellar agenesis. Molecular brain 19 32703236
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
2013 Yin Yang 1 (YY1) synergizes with Smad7 to inhibit TGF-β signaling in the nucleus. Science China. Life sciences 19 24369345
2011 Yin Yang 1 expression and localisation in quadriceps muscle in COPD. Archivos de bronconeumologia 19 21565439
2011 Overexpression of Yin Yang 1 in the pathogenesis of human hematopoietic malignancies. Critical reviews in oncogenesis 19 22248059
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 18 38165927
2020 YY1 promotes SOCS3 expression to inhibit STAT3‑mediated neuroinflammation and neuropathic pain. Molecular medicine reports 18 33300076
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
2008 Yin yang 1 directly regulates the transcription of RE-1 silencing transcription factor. Journal of neuroscience research 17 18092359
2024 RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding. Journal of experimental & clinical cancer research : CR 16 38163890
2024 YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance. Cancer cell international 16 38347631
2022 YY1 transcription factor induces proliferation and aerobic glycolysis of neuroblastoma cells via LDHA regulation. Experimental and therapeutic medicine 15 36569438
2022 Crosstalk between YY1 and lncRNAs in cancer: A review. Medicine 15 36626426
2017 YY1 Expression Is Sufficient for the Maintenance of Cardiac Progenitor Cell State. Stem cells (Dayton, Ohio) 15 28580685
2015 Yin-Yang 1 and Yin-Yang 2 exert opposing effects on the promoter activity of interleukin 4. Archives of pharmacal research 15 26345265

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