RRC ID 60962
Author Rispal J, Baron L, Beaulieu JF, Chevillard-Briet M, Trouche D, Escaffit F.
Title The H2A.Z histone variant integrates Wnt signaling in intestinal epithelial homeostasis.
Journal Nat Commun
Abstract The Tip60/p400 chromatin-modifying complex, which is involved in the incorporation and post-translational modification of the H2A.Z histone variant, regulates cell proliferation and important signaling pathways, such as Wnt. Here, we study the involvement of H2A.Z in intestinal epithelial homeostasis, which is dependent on the finely-tuned equilibrium between stem cells renewal and differentiation, under the control of such pathway. We use cell models and inducible knock-out mice to study the impact of H2A.Z depletion on intestinal homeostasis. We show that H2A.Z is essential for the proliferation of human cancer and normal intestinal crypt cells and negatively controls the expression of a subset of differentiation markers, in cultured cells and mice. H2A.Z impairs the recruitment of the intestine-specific transcription factor CDX2 to chromatin, is itself a target of the Wnt pathway and thus, acts as an integrator for Wnt signaling in the control of intestinal epithelial cell fate and homeostasis.
Volume 10(1)
Pages 1827
Published 2019-4-23
DOI 10.1038/s41467-019-09899-z
PII 10.1038/s41467-019-09899-z
PMID 31015444
PMC PMC6478875
MeSH Animals CDX2 Transcription Factor / genetics CDX2 Transcription Factor / metabolism Caco-2 Cells Cell Differentiation / genetics Cell Proliferation / genetics Chromatin / genetics Epithelial Cells / physiology Gene Expression Regulation / physiology HCT116 Cells Histones / genetics Histones / metabolism* Homeostasis / genetics* Humans Intestinal Mucosa / cytology Intestinal Mucosa / physiology* Male Mice Mice, Inbred C57BL Mice, Knockout Protein Isoforms / genetics Protein Isoforms / metabolism Wnt Signaling Pathway / genetics*
IF 12.121
Times Cited 5
Mice RBRC05765