Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination
More about Open Access at the CrickAuthors list
S Alexandra Garcia-Moreno Christopher R Futtner Isabella M Salamone Nitzan Gonen Robin Lovell-Badge Danielle M MaatoukAbstract
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.
Journal details
Journal Developmental Biology
Volume 446
Issue number 2
Pages 168-179
Publication date
Full text links
Publisher website (DOI) 10.1016/j.ydbio.2018.12.023
Figshare View on figshare
Europe PubMed Central 30594505
Pubmed 30594505
Keywords
Related topics
Type of publication