Polycomb repressive complex 2 impedes intestinal cell terminal differentiation.

TitlePolycomb repressive complex 2 impedes intestinal cell terminal differentiation.
Publication TypeJournal Article
Year of Publication2012
AuthorsBenoit YD, Lepage MB, Khalfaoui T, Tremblay E, Basora N, Carrier JC, Gudas LJ, Beaulieu J-F
JournalJ Cell Sci
Volume125
IssuePt 14
Pagination3454-63
Date Published2012 Jul 15
ISSN1477-9137
KeywordsCaco-2 Cells, Cell Differentiation, Cell Growth Processes, Cells, Cultured, Gastrointestinal Tract, Gene Expression Regulation, Developmental, Histones, Humans, Polycomb Repressive Complex 2, Promoter Regions, Genetic, Transcription, Genetic
Abstract

The crypt-villus axis constitutes the functional unit of the small intestine, where mature absorptive cells are confined to the villi, and stem cells and transit amplifying and differentiating cells are restricted to the crypts. The polycomb group (PcG) proteins repress differentiation and promote self-renewal in embryonic stem cells. PcGs prevent transcriptional activity by catalysing epigenetic modifications, such as the covalent addition of methyl groups on histone tails, through the action of the polycomb repressive complex 2 (PRC2). Although a role for PcGs in the preservation of stemness characteristics is now well established, recent evidence suggests that they may also be involved in the regulation of differentiation. Using intestinal epithelial cell models that recapitulate the enterocytic differentiation programme, we generated a RNAi-mediated stable knockdown of SUZ12, which constitutes a cornerstone for PRC2 assembly and functionality, in order to analyse intestinal cell proliferation and differentiation. Expression of SUZ12 was also investigated in human intestinal tissues, revealing the presence of SUZ12 in most proliferative epithelial cells of the crypt and an increase in its expression in colorectal cancers. Moreover, PRC2 disruption led to a significant precocious expression of a number of terminal differentiation markers in intestinal cell models. Taken together, our data identified a mechanism whereby PcG proteins participate in the repression of the enterocytic differentiation program, and suggest that a similar mechanism exists in situ to slow down terminal differentiation in the transit amplifying cell population.

DOI10.1242/jcs.102061
Alternate JournalJ. Cell. Sci.
PubMed ID22467857
PubMed Central IDPMC3516381
Grant ListR01 CA043796 / CA / NCI NIH HHS / United States
R01 DE010389 / DE / NIDCR NIH HHS / United States
MOP-123415 / / Canadian Institutes of Health Research / Canada
R01 CA0043796-22 / CA / NCI NIH HHS / United States