Gene Symbol: H2afx
Description: H2A histone family, member X
Alias: RGD1566119, H2A histone family, member X
Species: rat
Products:     H2afx

Top Publications

  1. Celeste A, Petersen S, Romanienko P, Fernandez Capetillo O, Chen H, Sedelnikova O, et al. Genomic instability in mice lacking histone H2AX. Science. 2002;296:922-7 pubmed
    ..Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA. ..
  2. Baarends W, Wassenaar E, van der Laan R, Hoogerbrugge J, Sleddens Linkels E, Hoeijmakers J, et al. Silencing of unpaired chromatin and histone H2A ubiquitination in mammalian meiosis. Mol Cell Biol. 2005;25:1041-53 pubmed
    ..This silencing in mammalian meiotic prophase cells concerns unpaired chromatin regions and resembles a phenomenon described for the fungus Neurospora crassa and named meiotic silencing by unpaired DNA. ..
  3. Pospelova T, Demidenko Z, Bukreeva E, Pospelov V, Gudkov A, Blagosklonny M. Pseudo-DNA damage response in senescent cells. Cell Cycle. 2009;8:4112-8 pubmed
    ..Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells. ..
  4. Yang F, Eckardt S, Leu N, McLaughlin K, Wang P. Mouse TEX15 is essential for DNA double-strand break repair and chromosomal synapsis during male meiosis. J Cell Biol. 2008;180:673-9 pubmed publisher
    ..Based on these data, we propose that TEX15 regulates the loading of DNA repair proteins onto sites of DSBs and, thus, its absence causes a failure in meiotic recombination. ..
  5. Oleson B, Broniowska K, Schreiber K, Tarakanova V, Corbett J. Nitric oxide induces ataxia telangiectasia mutated (ATM) protein-dependent ?H2AX protein formation in pancreatic ? cells. J Biol Chem. 2014;289:11454-64 pubmed publisher
    ..These findings show that the formation of DNA double strand breaks correlates with ATM activation, irreversible DNA damage, and ATM-dependent induction of apoptosis in cytokine-treated ? cells. ..
  6. Crowe S, Tsukerman S, Gale K, Jorgensen T, KONDRATYEV A. Phosphorylation of histone H2A.X as an early marker of neuronal endangerment following seizures in the adult rat brain. J Neurosci. 2011;31:7648-56 pubmed publisher
    ..This demonstrates that DNA DSB damage is an especially sensitive indicator of neuronal endangerment and that it is responsive to neuroprotective intervention. ..
  7. Kumar R, Bourbon H, de Massy B. Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice. Genes Dev. 2010;24:1266-80 pubmed publisher
  8. Polci R, Peng A, Chen P, Riley D, Chen Y. NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response. Cancer Res. 2004;64:8800-3 pubmed
    ..These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway. ..
  9. Saunders P, Turner J, Ruggiu M, Taggart M, Burgoyne P, Elliott D, et al. Absence of mDazl produces a final block on germ cell development at meiosis. Reproduction. 2003;126:589-97 pubmed
    ..It was concluded that in the absence of Dazl, germ cells can complete mitosis, and embark on functional differentiation but that, in both sexes, progression through meiotic prophase requires this RNA binding protein. ..

More Information


  1. Boehler C, Gauthier L, Mortusewicz O, Biard D, Saliou J, Bresson A, et al. Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. Proc Natl Acad Sci U S A. 2011;108:2783-8 pubmed publisher
    ..Both functions open stimulating prospects for specifically targeting PARP3 in cancer therapy. ..
  2. Lian I, Kim J, Okazawa H, Zhao J, Zhao B, Yu J, et al. The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes Dev. 2010;24:1106-18 pubmed publisher
    ..Moreover, YAP binds directly to promoters of a large number of genes known to be important for stem cells and stimulates their expression. Our observations establish a critical role of YAP in maintaining stem cell pluripotency. ..
  3. Sun X, Brieño Enríquez M, Cornelius A, Modzelewski A, Maley T, Campbell Peterson K, et al. FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice. Chromosoma. 2016;125:237-52 pubmed publisher
  4. Herbig U, Jobling W, Chen B, Chen D, Sedivy J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14:501-13 pubmed
    ..Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals. ..
  5. Rezacova M, Cap J, Vokurkova D, Lukasova E, Vavrova J, Cerman J, et al. Effect of somatostatin on repair of ionizing radiation-induced DNA damage in pituitary adenoma cells GH3. Physiol Res. 2008;57:225-35 pubmed
    ..In spite of this, large number of unrepaired DSB persists for 24 h after the treatment. We conclude that SS14 does not have a radioprotective effect on somatomammotroph GH3 cells. ..
  6. Maze I, Noh K, Soshnev A, Allis C. Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nat Rev Genet. 2014;15:259-71 pubmed publisher
  7. Shi Y, Zhuang X, Xu B, Hua J, Liao S, Shi Q, et al. SYCP3-like X-linked 2 is expressed in meiotic germ cells and interacts with synaptonemal complex central element protein 2 and histone acetyltransferase TIP60. Gene. 2013;527:352-9 pubmed publisher
    ..These results suggest that SLX2 might be involved in DNA recombination, synaptonemal complex formation as well as sex body maintenance during meiosis. ..
  8. Mihola O, Trachtulec Z, Vlcek C, Schimenti J, Forejt J. A mouse speciation gene encodes a meiotic histone H3 methyltransferase. Science. 2009;323:373-5 pubmed publisher
    ..These defects, seen also in Prdm9-null mutants, are rescued by the Prdm9 transgene. Identification of a vertebrate hybrid sterility gene reveals a role for epigenetics in speciation and opens a window to a hybrid sterility gene network. ..
  9. Kogo H, Tsutsumi M, Inagaki H, Ohye T, Kiyonari H, Kurahashi H. HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity. Genes Cells. 2012;17:897-912 pubmed publisher
    ..Our results thus show a HORMAD2-dependent quality control mechanism that recognizes unsynapsis and recruits ATR activity during mammalian meiosis. ..
  10. Pina B, Suau P. Changes in histones H2A and H3 variant composition in differentiating and mature rat brain cortical neurons. Dev Biol. 1987;123:51-8 pubmed
    ..Values of 65 days or less and 142 days were found for H2A.1 and H3.2, respectively. The preferential replacement of H2A.1 over H3.2 reinforces the view that the histone core does not degrade as a single unit. ..
  11. Reynard L, Turner J, Cocquet J, Mahadevaiah S, Touré A, Hoog C, et al. Expression analysis of the mouse multi-copy X-linked gene Xlr-related, meiosis-regulated (Xmr), reveals that Xmr encodes a spermatid-expressed cytoplasmic protein, SLX/XMR. Biol Reprod. 2007;77:329-35 pubmed
    ..As a result of these findings, the gene previously known as Xmr is now officially know as Slx, Sycp3-like, X-linked. ..
  12. Crowe S, Movsesyan V, Jorgensen T, Kondratyev A. Rapid phosphorylation of histone H2A.X following ionotropic glutamate receptor activation. Eur J Neurosci. 2006;23:2351-61 pubmed
  13. Lopez M, Tollervey J, Krastins B, Garces A, Sarracino D, Prakash A, et al. Depletion of nuclear histone H2A variants is associated with chronic DNA damage signaling upon drug-evoked senescence of human somatic cells. Aging (Albany NY). 2012;4:823-42 pubmed
    ..We propose that changes in the histone biosynthesis and chromatin assembly may directly contribute to cellular aging. In addition, we also outline the method that allows for quantitative and unbiased measurement of these changes. ..
  14. Artus C, Boujrad H, Bouharrour A, Brunelle M, Hoos S, Yuste V, et al. AIF promotes chromatinolysis and caspase-independent programmed necrosis by interacting with histone H2AX. EMBO J. 2010;29:1585-99 pubmed publisher
    ..Overall, our data shed new light in the mechanisms regulating programmed necrosis, elucidate a key nuclear partner of AIF, and uncover an AIF apoptogenic motif. ..
  15. Medina R, van der Deen M, Miele Chamberland A, Xie R, Van Wijnen A, Stein J, et al. The HiNF-P/p220NPAT cell cycle signaling pathway controls nonhistone target genes. Cancer Res. 2007;67:10334-42 pubmed
    ..We conclude that, in addition to histone genes, HiNF-P also regulates expression of nonhistone targets that influence competency for cell cycle progression. ..
  16. Beyret E, Lin H. Pinpointing the expression of piRNAs and function of the PIWI protein subfamily during spermatogenesis in the mouse. Dev Biol. 2011;355:215-26 pubmed publisher
    ..These results pinpoint a function of the PIWI protein subfamily to meiosis during spermatogenesis. ..
  17. Pelzel H, Schlamp C, Waclawski M, Shaw M, Nickells R. Silencing of Fem1cR3 gene expression in the DBA/2J mouse precedes retinal ganglion cell death and is associated with histone deacetylase activity. Invest Ophthalmol Vis Sci. 2012;53:1428-35 pubmed publisher
    ..This process can be ameliorated, but not completely blocked, using HDAC inhibitors. Epigenetic changes to active chromatin, such as deacetylation, may be mediated by HDAC3 in dying neurons. ..
  18. Panier S, Durocher D. Push back to respond better: regulatory inhibition of the DNA double-strand break response. Nat Rev Mol Cell Biol. 2013;14:661-72 pubmed publisher
  19. Ryu K, Sinnar S, Reinholdt L, Vaccari S, Hall S, Garcia M, et al. The mouse polyubiquitin gene Ubb is essential for meiotic progression. Mol Cell Biol. 2008;28:1136-46 pubmed
  20. Paul C, Povey J, Lawrence N, Selfridge J, Melton D, Saunders P. Deletion of genes implicated in protecting the integrity of male germ cells has differential effects on the incidence of DNA breaks and germ cell loss. PLoS ONE. 2007;2:e989 pubmed
    ..These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility. ..
  21. Hori T, Gardner L, Hata T, Chen F, Baine A, Uemoto S, et al. Pretreatment of liver grafts in vivo by ?-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat. Ann Transplant. 2013;18:299-313 pubmed publisher
    ..A specific agonist demonstrated regulation of GABAR in vivo in the liver. This activation in vivo reduced OS after OLT via the ATM/H2AX pathway. ..
  22. Zhang S, Hemmerich P, Grosse F. Werner syndrome helicase (WRN), nuclear DNA helicase II (NDH II) and histone gammaH2AX are localized to the centrosome. Cell Biol Int. 2007;31:1109-21 pubmed
  23. Zarybnicka L, Vavrova J, Havelek R, Tichy A, Pejchal J, Sinkorova Z. Lymphocyte subsets and their H2AX phosphorylation in response to in vivo irradiation in rats. Int J Radiat Biol. 2013;89:110-7 pubmed publisher
  24. Luangpraseuth Prosper A, Lesueur E, Jouneau L, Pailhoux E, Cotinot C, Mandon Pépin B. TOPAZ1, a germ cell specific factor, is essential for male meiotic progression. Dev Biol. 2015;406:158-71 pubmed publisher
    ..Our results also showed that 10% of these transcripts are long non-coding RNA. This suggests that a highly regulated balance of lncRNAs seems to be essential during spermatogenesis for induction of appropriate male gamete production. ..
  25. Guiraldelli M, Eyster C, Wilkerson J, Dresser M, Pezza R. Mouse HFM1/Mer3 is required for crossover formation and complete synapsis of homologous chromosomes during meiosis. PLoS Genet. 2013;9:e1003383 pubmed publisher
    ..We propose that initial steps of recombination are sufficient to support homology recognition, pairing, and initial chromosome synapsis and that HFM1 is required to form normal numbers of COs and to complete synapsis. ..
  26. Chen Y, Yang C, Zhen Y, Wallace C, Yang J, Sun C, et al. Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury. Stem Cell Res Ther. 2013;4:62 pubmed publisher
    ..05 for inter-group comparisons). Combination therapy using CsA plus ADMSCs offers improved protection against acute IR kidney injury. ..
  27. Lovren F, Pan Y, Quan A, Singh K, Khan R, Gupta N, et al. BRCA1 shields vascular smooth muscle cells from oxidative stress. J Thorac Cardiovasc Surg. 2014;147:1946-55, 1955.e1 pubmed publisher
    ..Gene- and/or cell-based approaches that improve BRCA1 bioavailability may represent a new approach in the treatment of diverse vascular diseases associated with an aberrant VSMC phenotype. ..
  28. Chang I, Kim J, Park K, Yoon S. Experimental varicocele induces p53-dependent germ cell apoptosis through activation of ?-H2AX. Urol Int. 2010;85:216-20 pubmed publisher
  29. Tarasenko N, Cutts S, Phillips D, Inbal A, Nudelman A, Kessler Icekson G, et al. Disparate impact of butyroyloxymethyl diethylphosphate (AN-7), a histone deacetylase inhibitor, and doxorubicin in mice bearing a mammary tumor. PLoS ONE. 2012;7:e31393 pubmed publisher
    ..In the myocardium, Dox suppressed these markers, whereas AN-7+Dox restored their expression. In conclusion, the combination of AN-7 and Dox results in two beneficial effects, improved anticancer efficacy and cardioprotection. ..
  30. Chadwick B, Willard H. Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant. Hum Mol Genet. 2001;10:1101-13 pubmed
    ..This study provides further information about the nucleosomal composition of chromatin on the inactive X chromosome and indicates that a number of H2A variants are non-randomly distributed on the active and inactive X chromosomes. ..
  31. Raz L, Zhang Q, Zhou C, Han D, Gulati P, Yang L, et al. Role of Rac1 GTPase in NADPH oxidase activation and cognitive impairment following cerebral ischemia in the rat. PLoS ONE. 2010;5:e12606 pubmed publisher
  32. Thompson C, Seiter J, Chappell M, Tappero R, Proctor D, Suh M, et al. Synchrotron-based imaging of chromium and γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water. Toxicol Sci. 2015;143:16-25 pubmed publisher
  33. Luo M, Zhou J, Leu N, Abreu C, Wang J, Anguera M, et al. Polycomb protein SCML2 associates with USP7 and counteracts histone H2A ubiquitination in the XY chromatin during male meiosis. PLoS Genet. 2015;11:e1004954 pubmed publisher
    ..Our results demonstrate that the SCML2/USP7 complex constitutes a novel molecular pathway in modulating the epigenetic state of sex chromosomes during male meiosis. ..
  34. Finsterbusch F, Ravindranathan R, Dereli I, Stanzione M, Tränkner D, Toth A. Alignment of Homologous Chromosomes and Effective Repair of Programmed DNA Double-Strand Breaks during Mouse Meiosis Require the Minichromosome Maintenance Domain Containing 2 (MCMDC2) Protein. PLoS Genet. 2016;12:e1006393 pubmed publisher
  35. Bhatti S, Kozlov S, Farooqi A, Naqi A, Lavin M, Khanna K. ATM protein kinase: the linchpin of cellular defenses to stress. Cell Mol Life Sci. 2011;68:2977-3006 pubmed publisher
    ..In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients...
  36. Meistrich M, Bucci L, Trostle Weige P, Brock W. Histone variants in rat spermatogonia and primary spermatocytes. Dev Biol. 1985;112:230-40 pubmed
    ..While TH2A and TH2B are already present and actively synthesized in early primary spermatocytes (around the preleptotene stage), H1t does not accumulate until the pachytene stage. ..
  37. Cook P, Ju B, Telese F, Wang X, Glass C, Rosenfeld M. Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions. Nature. 2009;458:591-6 pubmed publisher
  38. Kimura M, Fujii Y, Yamamoto R, Yafune A, Hayashi S, Suzuki K, et al. Involvement of multiple cell cycle aberrations in early preneoplastic liver cell lesions by tumor promotion with thioacetamide in a two-stage rat hepatocarcinogenesis model. Exp Toxicol Pathol. 2013;65:979-88 pubmed publisher
  39. Vaites L, Lee E, Lian Z, Barbash O, Roy D, Wasik M, et al. The Fbx4 tumor suppressor regulates cyclin D1 accumulation and prevents neoplastic transformation. Mol Cell Biol. 2011;31:4513-23 pubmed publisher
    ..Collectively, these data reveal a requisite role for the SCF(Fbx4) E3 ubiquitin ligase in regulating cyclin D1 accumulation, consistent with tumor suppressive function in vivo. ..
  40. Llano E, Herrán Y, García Tuñón I, Gutiérrez Caballero C, de Alava E, Barbero J, et al. Meiotic cohesin complexes are essential for the formation of the axial element in mice. J Cell Biol. 2012;197:877-85 pubmed publisher
  41. Saferali A, Berlivet S, Schimenti J, Bartolomei M, Taketo T, Naumova A. Defective imprint resetting in carriers of Robertsonian translocation Rb (8.12). Mamm Genome. 2010;21:377-87 pubmed publisher
    ..Furthermore, our findings support the notion that imprint establishment at the H19 locus extends into pachynema...
  42. Richter K, Brar S, Ray M, Pisitkun P, Bolland S, Verkoczy L, et al. Speckled-like pattern in the germinal center (SLIP-GC), a nuclear GTPase expressed in activation-induced deaminase-expressing lymphomas and germinal center B cells. J Biol Chem. 2009;284:30652-61 pubmed publisher
    ..These results strongly suggest that SLIP-GC is a replication-related protein in germinal center B cells whose reduction is toxic to cells through an AID-dependent mechanism. ..
  43. Tang M, Jacobs S, Mattiske D, Soh Y, Graham A, Tran A, et al. Contribution of the two genes encoding histone variant h3.3 to viability and fertility in mice. PLoS Genet. 2015;11:e1004964 pubmed publisher
    ..3 deficiency. They also reveal partial redundancy in function of H3f3a and H3f3b, with the latter gene being generally the most important. ..
  44. Reynard L, Cocquet J, Burgoyne P. The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant spermatid protein that interacts with a histone acetyltransferase and an acrosomal protein. Biol Reprod. 2009;81:250-7 pubmed publisher
    ..Together, these data suggest SLY1 may be involved in multiple processes during spermiogenesis, including the control of gene expression and the development or function of the acrosome...
  45. Soper S, van der Heijden G, Hardiman T, Goodheart M, Martin S, de Boer P, et al. Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis. Dev Cell. 2008;15:285-97 pubmed publisher
    ..This study demonstrates that MAEL, a nuage component, is indispensable for the silencing of TEs and identifies the initiation of meiosis as an important step in TE control in the male germline. ..
  46. Baban B, Liu J, Mozaffari M. Pressure overload regulates expression of cytokines, ?H2AX, and growth arrest- and DNA-damage inducible protein 153 via glycogen synthase kinase-3? in ischemic-reperfused hearts. Hypertension. 2013;61:95-104 pubmed publisher
    ..In conclusion, pressure overload, via a GSK-3?-dependent mechanism, exacerbates cell death in the isolated ischemic-reperfused heart involving regulation of inflammatory response, DNA injury, and GADD153 expression. ..
  47. Cho B, Ryu H, So Y, Jin C, Baek J, Park K, et al. Hepatoprotective effect of 2,3-dehydrosilybin on carbon tetrachloride-induced liver injury in rats. Food Chem. 2013;138:107-15 pubmed publisher
    ..Collectively, the present study suggests that DHS protects the liver from CCl(4)-induced hepatic damage via antioxidant and anti-inflammatory mechanisms. ..
  48. Evans E, Hogarth C, Evanoff R, Mitchell D, Small C, Griswold M. Localization and regulation of murine Esco2 during male and female meiosis. Biol Reprod. 2012;87:61 pubmed publisher
    ..ESCO2 colocalized with the gamma H2A histone family member X (H2AFX) in pachytene spermatocytes, indicating that ESCO2 is a component of the XY body...
  49. Tummala H, Kirwan M, Walne A, Hossain U, Jackson N, Pondarre C, et al. ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function. Am J Hum Genet. 2014;94:246-56 pubmed publisher
    ..Collectively, these observations identify a distinct bone-marrow-failure syndrome due to mutations in ERCC6L2, a gene implicated in DNA repair and mitochondrial function...
  50. Berkowitz K, Sowash A, Koenig L, Urcuyo D, Khan F, Yang F, et al. Disruption of CHTF18 causes defective meiotic recombination in male mice. PLoS Genet. 2012;8:e1002996 pubmed publisher
    ..These findings demonstrate essential roles for CHTF18 in mammalian spermatogenesis and meiosis, and suggest that CHTF18 may function during the double-strand break repair pathway to promote the formation of crossovers. ..
  51. Toyoda T, Cho Y, Akagi J, Mizuta Y, Hirata T, Nishikawa A, et al. Early Detection of Genotoxic Urinary Bladder Carcinogens by Immunohistochemistry for γ-H2AX. Toxicol Sci. 2015;148:400-8 pubmed publisher
    ..These results suggested that γ-H2AX may be a potential biomarker for the early detection of genotoxic bladder carcinogens. ..