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Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination
journal contributionposted on 2019-12-16, 11:59 authored by S Alexandra Garcia-Moreno, Christopher R Futtner, Isabella M Salamone, Nitzan Gonen, Robin Lovell-Badge, Danielle M Maatouk
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.
Cell differentiationChromatin landscapesEnhancersGonad developmentRegulatory elementsSex determinationAcetylationAnimalsChromatinFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGonadsHigh-Throughput Nucleotide SequencingHistonesMaleMice, Inbred C57BLMice, Inbred ICRMice, TransgenicRegulatory Sequences, Nucleic AcidSex Determination ProcessesLovell-Badge FC001107BRF-ack06 Biological Sciences11 Medical and Health SciencesDevelopmental Biology