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

S. Alexandra Garcia-Moreno, Christopher R. Futtner, Isabella M. Salamone, Nitzan Gonen, Robin Lovell-Badge, Danielle M. Maatouk

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)168-179
Number of pages12
JournalDevelopmental Biology
Volume446
Issue number2
DOIs
StatePublished - 15 Feb 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 The Authors

Keywords

  • Cell differentiation
  • Chromatin landscapes
  • Enhancers
  • Gonad development
  • Regulatory elements
  • Sex determination

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