Genome-wide identification of regulatory elements in Sertoli cells.

Published

Journal Article

A current goal of molecular biology is to identify transcriptional networks that regulate 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 genes enriched in Sertoli and pregranulosa cells; however, active enhancers marked by H3K27ac were enriched proximal to only Sertoli-enriched genes. Sequence analysis identified putative binding sites of known and novel transcription factors likely controlling Sertoli cell differentiation. As a validation of this approach, we identified a novel Sertoli cell 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 that underlies sex determination and identifies regions that potentially harbor non-coding mutations underlying disorders of sexual development.

Full Text

Duke Authors

Cited Authors

  • Maatouk, DM; Natarajan, A; Shibata, Y; Song, L; Crawford, GE; Ohler, U; Capel, B

Published Date

  • February 2017

Published In

Volume / Issue

  • 144 / 4

Start / End Page

  • 720 - 730

PubMed ID

  • 28087634

Pubmed Central ID

  • 28087634

Electronic International Standard Serial Number (EISSN)

  • 1477-9129

International Standard Serial Number (ISSN)

  • 0950-1991

Digital Object Identifier (DOI)

  • 10.1242/dev.142554

Language

  • eng