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Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination.

Developmental biology | 2019

Cis-regulatory elements are critical for the precise spatiotemporal regulation of genes during development. However, identifying functional regulatory sites that drive cell differentiation in vivo has been complicated by the high numbers of cells required for whole-genome epigenetic assays. Here, we identified putative regulatory elements during sex determination by performing ATAC-seq and ChIP-seq for H3K27ac in purified XX and XY gonadal supporting cells before and after sex determination in mice. We show that XX and XY supporting cells initiate sex determination with similar chromatin landscapes and acquire sex-specific regulatory elements as they commit to the male or female fate. To validate our approach, we identified a functional gonad-specific enhancer downstream of Bmp2, an ovary-promoting gene. This work increases our understanding of the complex regulatory network underlying mammalian sex determination and provides a powerful resource for identifying non-coding regulatory elements that could harbor mutations that lead to Disorders of Sexual Development.

Pubmed ID: 30594505 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: Cancer Research UK, United Kingdom
    Id: FC001107
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007169
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008061
  • Agency: Wellcome Trust, United Kingdom
    Id: FC001107
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: MC_U117562207

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Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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RRID:SCR_002037

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RRID:SCR_010881

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