Session: OR06-Molecular Mechanisms of Estrogen Action and Androgen Synthesis
Room 256 (Moscone Center)
Rui Li, Minho Chae, Miao Sun, Shino Murakami, and W. Lee Kraus
1 Signaling and Gene Regulation Laboratory, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390.
2 Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, 75390.
Estrogen signaling plays key roles in a wide array of physiological processes and disease states. Many of these effects are through the gene regulatory actions of estrogen, which acts through estrogen receptor protein to induce genome-wide alterations in the expression of protein-coding and non-coding genes. We are using a variety of gene-specific and genomic approaches in MCF-7 human breast cancer cells to examine the effects of estrogen signaling on the production of antisense transcripts. We have used Global Run-On and sequencing (GRO-seq), a genomic approach that maps the location and direction of all active RNA polymerases, combined with de novo transcript calling, to identify about ~1,200 antisense transcription units. We have also used RNA-seq to detect the steady-state RNAs that are produced from these transcription units, as well as their exon/intron structure. Little is known about antisense transcription in mammalian cells and the mechanisms by which it may affect sense gene expression or biological processes are poorly understood. Our results indicate that sense and antisense transcription are largely co-regulated in similar direction and magnitude upon estrogen treatment. From gene specific studies, we have found two novel antisense RNAs originating from the MYC locus, which may be implicated in breast cancer biology. We are characterizing these antisense RNAs by cloning and ASO-mediated knockdown. We are also examining their potential biological roles in human breast cancer cells. These studies will shed new light on the structure, function, and regulation of antisense transcripts.
Nothing to Disclose: RL, MC, MS, SM, WLK
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