Characterization of basal and estrogen-regulated antisense transcription in breast cancer cells: Role in regulating sense transcription
Characterization of basal and estrogen-regulated antisense transcription in breast cancer cells: Role in regulating sense transcription
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DOI：
10.1016/j.mce.2020.110746
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发表时间：
2020-04-15
影响因子：
4.1
通讯作者：
Kraus, W. Lee
中科院分区：
文献类型：
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作者：
Hou, Tim Y.;Nandu, Tulip;Kraus, W. Lee
雌激素响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的转录（即，基因），包括产生编码和非编码义的那些（例如，mRNA，lncRNA）和反义（即，asRNA）转录物。我们以前的特点是全球基础和雌激素调节转录组雌激素受体α（ER α）阳性MCF-7乳腺癌细胞。在此，我们已经挖掘了基因组数据，以根据其反义转录终止位点相对于其同源正义mRNA和lncRNA基因的位置来定义MCF-7细胞中的三类反义转录。这三个类别的不同之处在于它们对雌激素治疗的反应、与活性启动子（H3 K4 me 3、RNA聚合酶II、开放染色质结构）相关的许多基因组特征的富集以及它们的同源有义基因的生物学功能，如通过大卫基因本体分析的。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，表明这些反义转录物是5 '-加帽的，3'-聚腺苷酸化的，并且定位于细胞的不同隔室。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，揭示了另一层的雌激素调节的基因调控。
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 (ER alpha)-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.