CHARGE syndrome-associated proteins FAM172A and CHD7 influence male sex determination and differentiation through transcriptional and alternative splicing mechanisms.

ABSTRACT: To gain further insight into chromatin-mediated regulation of mammalian sex determination, we analyzed the role of the CHARGE syndrome-associated proteins FAM172A and CHD7. This study is based on our prior discoveries that a subset of corresponding mutant mice display complete male-to-female sex reversal, and that both of these proteins regulate co-transcriptional alternative splicing in neural crest cells. Here, we report that FAM172A and CHD7 are present in the developing gonads when sex determination normally occurs in mice. The interactome of FAM172A in pre-Sertoli cells again suggests a role at the chromatin-spliceosome interface, like in neural crest cells. Accordingly, analysis of Fam172a-mutant pre-Sertoli cells revealed transcriptional and splicing dysregulation of hundreds of gen

SUBMITTER: Belanger C 

PROVIDER: S-EPMC9304217 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature