Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol.
Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol.
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DOI：
10.1016/j.jmb.2013.01.022
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发表时间：
2013-10-09
影响因子：
5.6
通讯作者：
Mandal, Subhrangsu S.
中科院分区：
文献类型：
--
作者：
Bhan, Arunoday;Hussain, Imran;Ansari, Khairul I.;Kasiri, Sahba;Bashyal, Aarti;Mandal, Subhrangsu S.
HOTAIR是由12号染色体HOXC基因座的反义链转录而来的一种长的非编码RNA(LncRNA)。HOTAIR与染色质修饰酶协同作用，调节基因沉默。它在包括乳腺癌在内的多种癌症中都有过度表达。在此，我们证明了HOTAIR对细胞的生长和活力以及它的敲除诱导乳腺癌细胞的凋亡是至关重要的。我们还证明了HOTAIR是由雌二醇(E2)在转录水平上诱导的。其启动子含有多种功能性雌激素反应元件(ERE)。雌激素受体(ER)与组蛋白甲基酶MLL1、MLL3和CBP/p300等多种ER辅调节因子以E2依赖的方式与HOTAIR启动子结合。在E2存在的情况下，组蛋白H3K4三甲基化、组蛋白乙酰化和RNA聚合酶II募集的水平在HOTAIR启动子上得到丰富。ER和MLL的敲除下调了E2诱导的HOTAIR的表达。因此，与蛋白质编码基因的转录类似，E2诱导的反义转录产物HOTAIR的转录是通过ER和ER共同调节的，这种HOTAIR过表达的机制可能有助于乳腺癌的进展。
HOTAIR is a long noncoding RNA (lncRNA) that is transcribed from the antisense strand of HOXC 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 and MLL3 and CBP/p300 bind to the promoter of HOTAIR in an E2-dependent manner. Level of histone H3K4-trimethylation, histone acetylation and RNA polymerase II recruitment is enriched at the HOTAIR promoter in presence of E2. Knockdown of ERs and MLLs down regulated 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 over expression potentially contributes towards breast cancer progression.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
11.2
作者：
Dreijerink, Koen M. A.;Mulder, Klaas W.;Timmers, H. Th. Marc
通讯作者：
Timmers, H. Th. Marc
影响因子：
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作者：
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通讯作者：
Rinn, John L.
影响因子：
64.8
作者：
BARTOLOMEI, MS;ZEMEL, S;TILGHMAN, SM
通讯作者：
TILGHMAN, SM
影响因子：
5.3
作者：
Dreijerink, Koen M. A.;Varier, Radhika A.;Timmers, H. T. Marc
通讯作者：
Timmers, H. T. Marc