H2AFY explained

Core histone macro-H2A.1 is a protein that in humans is encoded by the H2AFY gene.^{[1] [2] [3]}

Function

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a member of the histone H2A family. It replaces conventional H2A histones in a subset of nucleosomes where it represses transcription and participates in stable X chromosome inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. Expression of these isoforms is associated to several cancers, such as hepatocellular carcinoma.^[4]

Further reading

• El Kharroubi A, Piras G, Zensen R, Martin MA . Transcriptional activation of the integrated chromatin-associated human immunodeficiency virus type 1 promoter . Molecular and Cellular Biology . 18 . 5 . 2535–44 . May 1998 . 9566873 . 110633 . 10.1128/mcb.18.5.2535.
• Costanzi C, Pehrson JR . Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals . Nature . 393 . 6685 . 599–601 . Jun 1998 . 9634239 . 10.1038/31275 . 1998Natur.393..599C . 205001095 .
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . Oct 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
• Deng L, de la Fuente C, Fu P, Wang L, Donnelly R, Wade JD, Lambert P, Li H, Lee CG, Kashanchi F . Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones . Virology . 277 . 2 . 278–95 . Nov 2000 . 11080476 . 10.1006/viro.2000.0593 . free .
• Chadwick BP, Willard HF . Histone H2A variants and the inactive X chromosome: identification of a second macroH2A variant . Human Molecular Genetics . 10 . 10 . 1101–13 . May 2001 . 11331621 . 10.1093/hmg/10.10.1101 . free .
• Deng L, Wang D, de la Fuente C, Wang L, Li H, Lee CG, Donnelly R, Wade JD, Lambert P, Kashanchi F . Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA . Virology . 289 . 2 . 312–26 . Oct 2001 . 11689053 . 10.1006/viro.2001.1129 . free .
• Chadwick BP, Willard HF . Cell cycle-dependent localization of macroH2A in chromatin of the inactive X chromosome . The Journal of Cell Biology . 157 . 7 . 1113–23 . Jun 2002 . 12082075 . 2173542 . 10.1083/jcb.200112074 .
• Takahashi I, Kameoka Y, Hashimoto K . MacroH2A1.2 binds the nuclear protein Spop . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1591 . 1–3 . 63–8 . Aug 2002 . 12183056 . 10.1016/S0167-4889(02)00249-5 .
• Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A, Mok SC, Randrianarison V, Brodie S, Salstrom J, Rasmussen TP, Klimke A, Marrese C, Marahrens Y, Deng CX, Feunteun J, Livingston DM . BRCA1 supports XIST RNA concentration on the inactive X chromosome . Cell . 111 . 3 . 393–405 . Nov 2002 . 12419249 . 10.1016/S0092-8674(02)01052-8 . 372211 . free .
• Angelov D, Molla A, Perche PY, Hans F, Côté J, Khochbin S, Bouvet P, Dimitrov S . The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling . Molecular Cell . 11 . 4 . 1033–41 . Apr 2003 . 12718888 . 10.1016/S1097-2765(03)00100-X . free .
• Behrends U, Schneider I, Rössler S, Frauenknecht H, Golbeck A, Lechner B, Eigenstetter G, Zobywalski C, Müller-Weihrich S, Graubner U, Schmid I, Sackerer D, Späth M, Goetz C, Prantl F, Asmuss HP, Bise K, Mautner J . Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries . International Journal of Cancer . 106 . 2 . 244–51 . Aug 2003 . 12800201 . 10.1002/ijc.11208 . 36836051 . free .
• Lusic M, Marcello A, Cereseto A, Giacca M . Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter . The EMBO Journal . 22 . 24 . 6550–61 . Dec 2003 . 14657027 . 291826 . 10.1093/emboj/cdg631 .
• Acín-Pérez R, Bayona-Bafaluy MP, Fernández-Silva P, Moreno-Loshuertos R, Pérez-Martos A, Bruno C, Moraes CT, Enríquez JA . Respiratory complex III is required to maintain complex I in mammalian mitochondria . Molecular Cell . 13 . 6 . 805–15 . Mar 2004 . 15053874 . 3164363 . 10.1016/S1097-2765(04)00124-8 .
• Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD . Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA . Developmental Cell . 8 . 1 . 19–30 . Jan 2005 . 15621527 . 10.1016/j.devcel.2004.10.019 . free .
• Hernández-Muñoz I, Lund AH, van der Stoop P, Boutsma E, Muijrers I, Verhoeven E, Nusinow DA, Panning B, Marahrens Y, van Lohuizen M . Stable X chromosome inactivation involves the PRC1 Polycomb complex and requires histone MACROH2A1 and the CULLIN3/SPOP ubiquitin E3 ligase . Proceedings of the National Academy of Sciences of the United States of America . 102 . 21 . 7635–40 . May 2005 . 15897469 . 1140410 . 10.1073/pnas.0408918102 . free .
• Ioudinkova ES, Barat A, Pichugin A, Markova E, Sklyar I, Pirozhkova I, Robin C, Lipinski M, Ogryzko V, Vassetzky YS, Razin SV . Distinct distribution of ectopically expressed histone variants H2A.Bbd and MacroH2A in open and closed chromatin domains . PLOS ONE . 7 . 10 . e47157 . 2012 . 23118866 . 3484066 . 10.1371/journal.pone.0047157 . 2012PLoSO...747157I . free .

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Core histone macro-H2A.1

Notes and References

1. Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z . Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning . Proceedings of the National Academy of Sciences of the United States of America . 95 . 14 . 8175–80 . Jul 1998 . 9653160 . 20949 . 10.1073/pnas.95.14.8175 . 1998PNAS...95.8175M . free .
2. Lee Y, Hong M, Kim JW, Hong YM, Choe YK, Chang SY, Lee KS, Choe IS . Isolation of cDNA clones encoding human histone macroH2A1 subtypes . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1399 . 1 . 73–7 . Jul 1998 . 9714746 . 10.1016/s0167-4781(98)00098-0 .
3. Web site: Entrez Gene: H2AFY H2A histone family, member Y.
4. Rappa F, Greco A, Podrini C, Cappello F, Foti M, Bourgoin L, Peyrou M, Marino A, Scibetta N, Williams R, Mazzoccoli G, Federici M, Pazienza V, Vinciguerra M . Immunopositivity for histone macroH2A1 isoforms marks steatosis-associated hepatocellular carcinoma . PLOS ONE . 8 . 1 . e54458 . 2013 . 23372727 . 3553099 . 10.1371/journal.pone.0054458 . 2013PLoSO...854458R . free .