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.

中文翻译：

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乳腺癌细胞中基础和雌激素调节的反义转录的表征：在调节有义转录中的作用。

雌激素反应性乳腺癌细胞同时具有基础和雌激素调节的转录程序，从而导致许多不同转录单位（即基因）的转录，包括产生编码和非编码义的转录单位（例如，mRNA，lncRNA）和反义（即asRNA）转录本。我们以前已经表征了雌激素受体α（ERα）阳性MCF-7乳腺癌细胞中的全球基础和雌激素调节的转录组。本文中，我们已挖掘基因组数据，以根据其反义转录终止位点相对于其同源有义mRNA和lncRNA基因的位置来定义MCF-7细胞中的三类反义转录。这三类药物对雌激素的反应，与活性启动子（H3K4me3，RNA聚合酶II，开放的染色质结构），以及它们的同源有义基因的生物学功能（通过DAVID基因本体分析）。我们进一步表征了MCF-7细胞中MYC基因产生的两个雌激素调节的反义转录物，显示这些反义转录物是5'端帽的，3'-聚腺苷酸的，并位于细胞的不同区室。总之，我们的分析揭示了与不同的生物过程和对雌激素刺激的反应相关的不同类别的反义转录，揭示了另一层激素调节的基因调节。我们进一步表征了MCF-7细胞中MYC基因产生的两个雌激素调节的反义转录物，显示这些反义转录物是5'端帽的，3'-聚腺苷酸的，并位于细胞的不同区室。总之，我们的分析揭示了与不同的生物过程和对雌激素刺激的反应相关的不同类别的反义转录，揭示了另一层激素调节的基因调节。我们进一步表征了MCF-7细胞中MYC基因产生的两个雌激素调节的反义转录物，显示这些反义转录物是5'端帽的，3'-聚腺苷酸的，并位于细胞的不同区室。总之，我们的分析揭示了与不同的生物过程和对雌激素刺激的反应相关的不同类别的反义转录，揭示了另一层激素调节的基因调节。