The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells

ABSTRACT: Lgr5+ intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5+ ISC self-renewal remain elusive. Here we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration. Mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter and induces expression of this transcription factor. By activating PPAR? expression, Prdm16 in turn initiates PPAR? signaling, which sustains ISC stemness. Rest or Prdm16 deficiency abrogate the self-renewal capacity of ISCs as well as intestinal epithelial regeneration. Collectively, these data show that the SRCAP-REST-Prdm16-PPAR? axis is required for self-renewal maintenance of Lgr5+ ISCs.

SUBMITTER: Dr. Buqing Ye 

PROVIDER: S-SCDT-EMBOJ-2019-103786 | biostudies-other |

REPOSITORIES: biostudies-other