Identifying direct targets of the DMRT transcription factor Doublesex

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NIDDK	GEN/GENOM-4

* FARE Award Winner

Authors

• E. Clough
• C. Whitworth
• E. Jimenez
• H. Pavlou
• L. Hempel
• M. Neville
• S. Goodwin
• M. Van Doren
• B. Oliver

Abstract

Identifying target genes of a transcription factor is essential for understanding how it directs developmental or disease processes. In order to understand a complete genetic pathway from transcription factor genomic binding sites to phenotype, we are identifying the target genes of Drosophila Doublesex (DSX), a DMRT (DSX/Mab-3-Related Transcription Factor) transcription factor family member that regulates sexual development in Drosophila and higher eukaryotes including mammals. We have used multiple genome-wide approaches to assay DSX occupancy across diverse developmental and chromatin contexts where dsx is expressed. These studies have yielded thousands of sites that are concentrated near transcriptional start sites and within introns. To identify genes whose transcription depends on DSX we have performed RNA-sequencing on multiple dsx-expressing tissues in which we have used the power of Drosophila genetics to alter DSX protein status between female and male isoforms that direct female or male sexual development, respectively. In order to make connections between target genes and phenotype, we are knocking down these genes specifically in dsx-expressing cells to evaluate their role in sexual differentiation. DSX target gene knockdown phenotypes reveal defects affecting specific aspects of sexual differentiation from sex-specific bristle structure and pigmentation, gonad morphogenesis to egg-laying capability.

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