title: An H2A histone isotype regulates estrogen receptor target genes by mediating enhancer-promoter-3'-UTR interactions in breast cancer cells.
abstract: A replication-dependent histone H2A isotype, H2ac, is upregulated in MCF-7 cells and in estrogen receptor-positive clinical breast cancer tissues. Cellular depletion of this H2A isotype leads to defective estrogen signaling, loss of cell proliferation and cell cycle arrest at G0/G1 phase. H2ac mediates regulation of estrogen receptor target genes, particularly BCL2 and c-MYC, by recruiting estrogen receptor alpha through its HAR domain and facilitating the formation of a chromatin loop between the promoter, enhancer and 3'-untranslated region of the respective genes. These findings reveal a new role for histone isotypes in the regulation of gene expression in cancer cells, and suggest that these molecules may be targeted for anti-cancer drug discovery.
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan, Republic of China, VYM Genome Research Center, National Yang-Ming University, University System of Taiwan, Taipei 11221, Taiwan, Republic of China and Chien-Tien Hsu Cancer Research Foundation, Taipei 11221, Taiwan, Republic of China.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Su
authors.forename: Tsai-Yu
authors.initials: TY
authors.lastname: Tzeng
authors.forename: Ching
authors.initials: C
authors.lastname: Cheng
authors.forename: Ming-Ta
authors.initials: MT
authors.lastname: Hsu
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry; D004742:Enhancer Elements, Genetic; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D016259:Genes, myc; D006657:Histones / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D002843:Chromatin; D047628:Estrogen Receptor alpha; D006657:Histones; D020033:Protein Isoforms; D004958:Estradiol