title: Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol.
abstract: HOTAIR (HOX antisense intergenic RNA) is a long noncoding RNA (lncRNA) that is transcribed from the antisense strand of homeobox C gene locus in chromosome 12. HOTAIR coordinates with chromatin-modifying enzymes and regulates gene silencing. It is overexpressed in various carcinomas including breast cancer. Herein, we demonstrated that HOTAIR is crucial for cell growth and viability and its knockdown induced apoptosis in breast cancer cells. We also demonstrated that HOTAIR is transcriptionally induced by estradiol (E2). Its promoter contains multiple functional estrogen response elements (EREs). Estrogen receptors (ERs) along with various ER coregulators such as histone methylases MLL1 (mixed lineage leukemia 1) and MLL3 and CREB-binding protein/p300 bind to the promoter of HOTAIR in an E2-dependent manner. Level of histone H3 lysine-4 trimethylation, histone acetylation, and RNA polymerase II recruitment is enriched at the HOTAIR promoter in the presence of E2. Knockdown of ERs and MLLs downregulated the E2-induced HOTAIR expression. Thus, similar to protein-coding gene transcription, E2-induced transcription of antisense transcript HOTAIR is coordinated via ERs and ER coregulators, and this mechanism of HOTAIR overexpression potentially contributes towards breast cancer progression.
authors: Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors: Arunoday
authors: A
authors: Bhan
authors: Imran
authors: I
authors: Hussain
authors: Khairul I
authors: KI
authors: Ansari
authors: Sahba
authors: S
authors: Kasiri
authors: Aarti
authors: A
authors: Bashyal
authors: Subhrangsu S
authors: SS
authors: Mandal
mesh_terms: D016375:Antisense Elements (Genetics) / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D046208:Microchip Analytical Procedures; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D014158:Transcription, Genetic
chemical_list: D016375:Antisense Elements (Genetics); D004268:DNA-Binding Proteins; C561566:HOTAIR long untranslated RNA, human; D006657:Histones; C497422:KMT2A protein, human; C452979:KMT2C protein, human; D062085:RNA, Long Noncoding; D011960:Receptors, Estrogen; D051788:Myeloid-Lymphoid Leukemia Protein; D004958:Estradiol; D011495:Histone-Lysine N-Methyltransferase; D050882:CREB-Binding Protein; C494363:CREBBP protein, human
keywords: 4′,6-diamidino-2-phenylindole; CBP; CREB-binding protein; ChIP; DAPI; DMEM; Dulbecco's modified Eagle's medium; E2; ER; ERE; FBS; H3 lysine-4; H3K27; H3K4; HOTAIR; HOX antisense intergenic RNA; HOXC; JAM2; MLL; MLL histone methylases; PBS; PCDHB5; PRC2; RNA polymerase II; RNAP II; TUNEL; chromatin immunoprecipitation; epigenetics; estradiol; estrogen receptor; estrogen receptors; estrogen response element; fetal bovine serum; histone H3 lysine 27; homeobox C; junction adhesion molecule 2; lncRNA; long noncoding RNA; mixed lineage leukemia; phosphate-buffered saline; polycomb repressive complex 2; protocadherin B5; siSENSE; small interfering sense; terminal dUTP nicked end labeling
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