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Showing H2AC20 — H2A is a alias.

H2AC20

Histone H2A type 2-C · UniProt Q16777

Length
129 aa
Mass
14.0 kDa
Annotated
2026-06-10
100 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

H2AC20 (Hist2h2ac/HIST2H2AC) is a canonical histone H2A isoform whose expression marks undifferentiated, proliferating mammary epithelial cells and operates as a downstream effector of EGF/EGFR signaling acting through the MEK1/2 and PI3-K pathways (PMID:28288875). Silencing of Hist2h2ac blocks EGF-induced Zeb-1 expression and prevents E-cadherin downregulation, and re-expression rescues these defects, placing this isoform within the epithelial-mesenchymal transition program; its knockdown also abolishes EGF-induced proliferation despite intact upstream EGFR/ERBB2/ERK1/2 activation, indicating it acts downstream of receptor signaling to drive proliferation and EMT (PMID:28288875). Beyond this single characterization in mammary epithelial cells, no further mechanism specific to this H2A isoform has been established in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2017 Medium

    Established that a specific canonical H2A isoform, rather than H2A variants generally, is selectively expressed in proliferating mammary epithelial cells and functions as a downstream effector of EGFR signaling driving EMT and proliferation.

    Evidence Mass spectrometry of histone levels during differentiation, siRNA silencing with re-expression rescue, and proliferation/EMT marker assays across HC11, EpH4, MC4-L2, and T47-D cell lines

    PMID:28288875

    Open questions at the time
    • No molecular mechanism by which a canonical histone isoform selectively controls Zeb-1/E-cadherin transcription is defined
    • Whether the phenotype reflects isoform-specific chromatin incorporation versus a non-canonical function is not resolved
    • Findings come from a single lab and cultured cell lines without in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How H2AC20 mechanistically links EGFR signaling output to the Zeb-1/E-cadherin transcriptional program remains unknown.
  • No chromatin localization or genomic occupancy data for this isoform
  • No post-translational modification or interacting-partner characterization
  • No structural or biochemical distinction from other H2A isoforms established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 1
Localization
GO:0000228 nuclear chromosome 1
Pathway
R-HSA-162582 Signal Transduction 1

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 The canonical histone H2A isoform Hist2h2ac (HIST2H2AC/H2AC20) is expressed specifically in undifferentiated/proliferating mammary epithelial cells and is downstream of EGF/EGFR signaling via MEK1/2 and PI3-K pathways. Silencing of Hist2h2ac inhibited EGF-induced Zeb-1 expression and prevented E-cadherin downregulation (epithelial-mesenchymal transition markers), an effect rescued by Hist2h2ac re-expression. Knockdown also blocked EGF-induced proliferation despite increased EGFR/ERBB2/ERK1/2 activation, placing Hist2h2ac downstream of EGFR signaling and as a regulator of oncogenic EMT and proliferation programs. Mass spectrometry screening of histone levels during differentiation; siRNA-mediated silencing; re-expression rescue; qRT-PCR; Western blot; cell proliferation assays in HC11, EpH4, MC4-L2, and T47-D cell lines Cancer letters Medium 28288875

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Histone H2A variants H2AX and H2AZ. Current opinion in genetics & development 592 11893489
2008 Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks. Nature 438 18815594
2008 WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 324 19092802
2019 The histone variant H2A.Z in gene regulation. Epigenetics & chromatin 252 31200754
2014 ANP32E is a histone chaperone that removes H2A.Z from chromatin. Nature 221 24463511
2008 H2A.Z: view from the top. Structure (London, England : 1993) 215 18275809
2012 Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation. Cell 169 23260146
2019 H2A.Z facilitates licensing and activation of early replication origins. Nature 146 31875854
2021 BARD1 reads H2A lysine 15 ubiquitination to direct homologous recombination. Nature 144 34321663
2017 INO80 exchanges H2A.Z for H2A by translocating on DNA proximal to histone dimers. Nature communications 120 28604691
2019 Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1. Cell cycle (Georgetown, Tex.) 119 30907299
2009 The beauty of being a variant: H2A.Z and the SWR1 complex in plants. Molecular plant 112 19825639
2010 Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis. Genome research 104 20709945
2013 USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15. Cell cycle (Georgetown, Tex.) 101 24196443
2009 Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates. BMC biology 91 20003410
2010 Reconciling the positive and negative roles of histone H2A.Z in gene transcription. Epigenetics 90 20364108
2008 The gamma-H2A.X: is it just a surrogate marker of double-strand breaks or much more? Environmental and molecular mutagenesis 90 18095327
2013 Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance. Biochimica et biophysica acta 88 24459731
2009 H2A.Z and H3.3 histone variants affect nucleosome structure: biochemical and biophysical studies. Biochemistry 87 19856965
2021 Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma. Nature 86 34349258
2018 The Histone Chaperone FACT Coordinates H2A.X-Dependent Signaling and Repair of DNA Damage. Molecular cell 84 30344095
2006 Patterning chromatin: form and function for H2A.Z variant nucleosomes. Current opinion in genetics & development 83 16503125
2016 Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1. Nature structural & molecular biology 82 26974124
2009 Acetylation of vertebrate H2A.Z and its effect on the structure of the nucleosome. Biochemistry 81 19385636
2015 H2A.Z: a molecular rheostat for transcriptional control. F1000prime reports 79 25705384
2016 H2A.Z controls the stability and mobility of nucleosomes to regulate expression of the LH genes. Nature communications 70 27653784
2016 Molecular basis and specificity of H2A.Z-H2B recognition and deposition by the histone chaperone YL1. Nature structural & molecular biology 68 26974126
2023 Histone variant H2A.Z modulates nucleosome dynamics to promote DNA accessibility. Nature communications 67 36765119
2021 The H2A.Z-nuclesome code in mammals: emerging functions. Trends in genetics : TIG 64 34702577
2016 The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition. Nature communications 63 26876487
2009 H2A.Bbd: an X-chromosome-encoded histone involved in mammalian spermiogenesis. Nucleic acids research 62 20008104
2013 The variant histone H2A.V of Drosophila--three roles, two guises. Chromosoma 60 23553272
2014 RNF168-mediated H2A neddylation antagonizes ubiquitylation of H2A and regulates DNA damage repair. Journal of cell science 59 24634510
1990 The human histone H2A.Z gene. Sequence and regulation. The Journal of biological chemistry 56 1697587
2022 Histone H2A variants: Diversifying chromatin to ensure genome integrity. Seminars in cell & developmental biology 52 35331626
2021 Histone variant H2A.Z regulates zygotic genome activation. Nature communications 52 34853314
2015 The DREAM complex promotes gene body H2A.Z for target repression. Genes & development 52 25737279
2015 H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast. eLife 52 26116819
2009 Histone variant H2A.Z regulates centromere silencing and chromosome segregation in fission yeast. The Journal of biological chemistry 50 19910462
2021 Structural basis of chromatin regulation by histone variant H2A.Z. Nucleic acids research 49 34643712
2016 SMYD3-Mediated H2A.Z.1 Methylation Promotes Cell Cycle and Cancer Proliferation. Cancer research 49 27569210
2019 Znhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation. Nature communications 48 30842416
2009 Transcriptional and epigenetic functions of histone variant H2A.Z. Biochemistry and cell biology = Biochimie et biologie cellulaire 48 19234520
2017 A new link between transcriptional initiation and pre-mRNA splicing: The RNA binding histone variant H2A.B. PLoS genetics 47 28234895
2018 Histone variant H2A.Z deposition and acetylation directs the canonical Notch signaling response. Nucleic acids research 44 29986055
2020 Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells. Nucleic acids research 42 32392318
2020 Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2. The EMBO journal 42 33073403
2021 Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells. Nature communications 41 33953180
2012 H2A.Z-dependent crosstalk between enhancer and promoter regulates cyclin D1 expression. Oncogene 41 23108396
2010 Histone variant H2A.Z can serve as a new target for breast cancer therapy. Current medicinal chemistry 41 20666725
2021 Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression. EMBO reports 40 34423893
2012 DNA methylation, H2A.Z, and the regulation of constitutive expression. Cold Spring Harbor symposia on quantitative biology 40 23250988
2020 Distinct roles for H4 and H2A.Z acetylation in RNA transcription in African trypanosomes. Nature communications 39 32198348
2008 Quickly evolving histones, nucleosome stability and chromatin folding: all about histone H2A.Bbd. Gene 39 18329190
2014 H2A-DUBbing the mammalian epigenome: expanding frontiers for histone H2A deubiquitinating enzymes in cell biology and physiology. The international journal of biochemistry & cell biology 38 24647359
2021 H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma. Oncogene 37 33627784
2023 Coordinated histone variant H2A.Z eviction and H3.3 deposition control plant thermomorphogenesis. The New phytologist 35 36647799
2021 H2A.X Phosphorylation in Oxidative Stress and Risk Assessment in Plasma Medicine. Oxidative medicine and cellular longevity 35 34938381
1999 The human H2A and H2B histone gene complement. Biological chemistry 33 10064132
2019 Gene editing of the multi-copy H2A.B gene and its importance for fertility. Genome biology 32 30704500
2022 Tip60-mediated H2A.Z acetylation promotes neuronal fate specification and bivalent gene activation. Molecular cell 31 36417913
2017 The histone H2A isoform Hist2h2ac is a novel regulator of proliferation and epithelial-mesenchymal transition in mammary epithelial and in breast cancer cells. Cancer letters 29 28288875
2022 Coordinated DNA and histone dynamics drive accurate histone H2A.Z exchange. Science advances 28 35263135
2014 Dynamics of histone variant H3.3 and its coregulation with H2A.Z at enhancers and promoters. Nucleus (Austin, Tex.) 28 24637397
2020 Variation on a theme: Evolutionary strategies for H2A.Z exchange by SWR1-type remodelers. Current opinion in cell biology 27 33217681
2019 The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis. Nature communications 27 31015444
2014 Histone H2A.Z deregulation in prostate cancer. Cause or effect? Cancer metastasis reviews 27 24398858
2013 DNA aptamers selectively target Leishmania infantum H2A protein. PloS one 27 24205340
2023 The HDAC6-RNF168 axis regulates H2A/H2A.X ubiquitination to enable double-strand break repair. Nucleic acids research 26 37503842
2015 Expression of Non-acetylatable H2A.Z in Myoblast Cells Blocks Myoblast Differentiation through Disruption of MyoD Expression. The Journal of biological chemistry 26 25839232
2012 Histone H2A (H2A.X and H2A.Z) variants in molluscs: molecular characterization and potential implications for chromatin dynamics. PloS one 26 22253857
2021 INO80 promotes H2A.Z occupancy to regulate cell fate transition in pluripotent stem cells. Nucleic acids research 25 34139016
2019 DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during transcription. Nature chemical biology 25 31527837
2018 H2A.Z regulates tumorigenesis, metastasis and sensitivity to cisplatin in intrahepatic cholangiocarcinoma. International journal of oncology 25 29532867
2009 Nonenzymatic biotinylation of histone H2A. Protein science : a publication of the Protein Society 25 19160459
2022 H2A.Z's 'social' network: functional partners of an enigmatic histone variant. Trends in biochemical sciences 24 35606214
2017 Histone H2A Monoubiquitination in Neurodevelopmental Disorders. Trends in genetics : TIG 24 28669576
2020 VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis. Cells 21 32708675
2023 The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy. Science advances 20 36888706
2019 USP28 regulates deubiquitination of histone H2A and cell proliferation. Experimental cell research 19 30910399
2022 Spotlight on histone H2A variants: From B to X to Z. Seminars in cell & developmental biology 18 35365397
2020 Vital and Distinct Roles of H2A.Z Isoforms in Hepatocellular Carcinoma. OncoTargets and therapy 18 32547065
2023 Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1. Molecular cell 17 37536340
2022 GAS41 mediates proliferation and GEM chemoresistance via H2A.Z.2 and Notch1 in pancreatic cancer. Cellular oncology (Dordrecht, Netherlands) 17 35503594
2023 The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs. Nature communications 16 36709316
2022 H2A.Z deposition by SWR1C involves multiple ATP-dependent steps. Nature communications 16 36396651
2021 Effects of H2A.B incorporation on nucleosome structures and dynamics. Biophysical journal 16 33609493
2021 Tip60 activates Hoxa9 and Meis1 expression through acetylation of H2A.Z, promoting MLL-AF10 and MLL-ENL acute myeloid leukemia. Leukemia 16 33967269
2020 Molecular mechanism of histone variant H2A.B on stability and assembly of nucleosome and chromatin structures. Epigenetics & chromatin 16 32664941
2020 Biparental contributions of the H2A.B histone variant control embryonic development in mice. PLoS biology 16 33362208
2017 Genome-wide identification of histone H2A and histone variant H2A.Z-interacting proteins by bPPI-seq. Cell research 16 28862252
2017 Redundant Functions for Nap1 and Chz1 in H2A.Z Deposition. Scientific reports 16 28883625
2022 Contribution of the histone variant H2A.Z to expression of responsive genes in plants. Seminars in cell & developmental biology 15 35474148
2020 Histone H2A.Z is required for androgen receptor-mediated effects on fear memory. Neurobiology of learning and memory 15 32916283
2018 Metformin alters H2A.Z dynamics and regulates androgen dependent prostate cancer progression. Oncotarget 15 30651935
2014 Yeast X-chromosome-associated protein 5 (Xap5) functions with H2A.Z to suppress aberrant transcripts. EMBO reports 15 24957674
2023 Mechanism of RanGTP priming H2A-H2B release from Kap114 in an atypical RanGTP•Kap114•H2A-H2B complex. Proceedings of the National Academy of Sciences of the United States of America 14 37450495
2022 Mammalian PERIOD2 regulates H2A.Z incorporation in chromatin to orchestrate circadian negative feedback. Nature structural & molecular biology 14 35606517
2021 Histone H2A.X phosphorylation and Caspase-Initiated Chromatin Condensation in late-stage erythropoiesis. Epigenetics & chromatin 14 34330317
2020 RNA-Guided Genomic Localization of H2A.L.2 Histone Variant. Cells 14 32085641

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