Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA; Program in Genetics, Development and Disease, Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Mol Cell Endocrinol. 2020 Apr 15;506:110746. doi: 10.1016/j.mce.2020.110746. Epub 2020 Feb 5.
Estrogen-responsive breast cancer cells exhibit both basal and estrogen-regulated transcriptional programs, which lead to the transcription of many different transcription units (i.e., genes), including those that produce coding and non-coding sense (e.g., mRNA, lncRNA) and antisense (i.e., asRNA) transcripts. We have previously characterized the global basal and estrogen-regulated transcriptomes in estrogen receptor alpha (ERα)-positive MCF-7 breast cancer cells. Herein, we have mined genomic data to define three classes of antisense transcription in MCF-7 cells based on where their antisense transcription termination sites reside relative to their cognate sense mRNA and lncRNA genes. These three classes differ in their response to estrogen treatment, the enrichment of a number of genomic features associated with active promoters (H3K4me3, RNA polymerase II, open chromatin architecture), and the biological functions of their cognate sense genes as analyzed by DAVID gene ontology. We further characterized two estrogen-regulated antisense transcripts arising from the MYC gene in MCF-7 cells, showing that these antisense transcripts are 5'-capped, 3'-polyadenylated, and localized to different compartments of the cell. Together, our analyses have revealed distinct classes of antisense transcription correlated to different biological processes and response to estrogen stimulation, uncovering another layer of hormone-regulated gene regulation.
雌激素反应性乳腺癌细胞表现出基础和雌激素调节的转录程序，这导致许多不同转录单位（即基因）的转录，包括那些产生编码和非编码有意义（例如，mRNA、lncRNA）和反义（即 asRNA）转录物的基因。我们之前已经描述了雌激素受体 alpha (ERα)-阳性 MCF-7 乳腺癌细胞中的全局基础和雌激素调节转录组。在此，我们通过挖掘基因组数据，根据其反义转录终止位点相对于其同源有意义 mRNA 和 lncRNA 基因的位置，将 MCF-7 细胞中的反义转录分为三类。这三类在对雌激素处理的反应、与活性启动子相关的许多基因组特征（H3K4me3、RNA 聚合酶 II、开放染色质结构）的富集以及它们同源有意义基因的生物学功能方面存在差异，这些功能是通过 DAVID 基因本体进行分析的。我们进一步描述了 MCF-7 细胞中 MYC 基因产生的两个雌激素调节的反义转录本，表明这些反义转录本 5'-加帽、3'-多聚腺苷酸化，并定位于细胞的不同区域。总之，我们的分析揭示了与不同生物学过程和对雌激素刺激的反应相关的不同反义转录类别，揭示了另一个受激素调节的基因调控层。
