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Genome-wide identification of regulatory elements in Sertoli cells

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Item Type:Article
Title:Genome-wide identification of regulatory elements in Sertoli cells
Creators Name:Maatouk, D.M. and Natarajan, A. and Shibata, Y. and Song, L. and Crawford, G.E. and Ohler, U. and Capel, B.
Abstract:A current goal of molecular biology is to identify transcriptional networks regulating cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and cell types are mixed. To identify regulatory sites during sex determination, we subjected Sertoli cells from mouse fetal testes to DNaseI-seq and ChIP-seq for H3K27ac. DNaseI-seq identified putative regulatory sites around Sertoli- and pregranulosa-enriched genes; however, active enhancers marked by H3K27ac were enriched proximal only to Sertoli-enriched genes. Sequence analysis identified putative binding sites of known and novel transcription factors likely controlling Sertoli differentiation. As a validation of this approach, we identified a novel Sertoli enhancer upstream of Wt1, and used it to drive expression of a transgenic reporter in Sertoli cells. This work furthers our understanding of the complex genetic network underlying sex determination and identifies regions potentially harboring non-coding mutations underlying Disorders of Sexual Development.
Keywords:Genome-Wise Enhancer Profiling, Sex Determination, Sertoli Cell Development, Animals, Mice
Source:Development
ISSN:0950-1991
Publisher:Company of Biologists (U.K.)
Volume:144
Number:4
Page Range:720-730
Date:15 February 2017
Official Publication:https://doi.org/10.1242/dev.142554
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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