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PRC 2 preserves intestinal progenitors and restricts secretory lineage commitment
Author(s) -
Chiacchiera Fulvio,
Rossi Alessandra,
Jammula SriGanesh,
Zanotti Marika,
Pasini Diego
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694550
Subject(s) - biology , progenitor cell , lineage (genetic) , progenitor , microbiology and biotechnology , genetics , gene , stem cell
Chromatin modifications shape cell heterogeneity by activating and repressing defined sets of genes involved in cell proliferation, differentiation and development. Polycomb‐repressive complexes ( PRC s) act synergistically during development and differentiation by maintaining transcriptional repression of common genes. PRC 2 exerts this activity by catalysing H3K27 trimethylation. Here, we show that in the intestinal epithelium PRC 2 is required to sustain progenitor cell proliferation and the correct balance between secretory and absorptive lineage differentiation programs. Using genetic models, we show that PRC 2 activity is largely dispensable for intestinal stem cell maintenance but is strictly required for radiation‐induced regeneration by preventing Cdkn2a transcription. Combining these models with genomewide molecular analysis, we further demonstrate that preferential accumulation of secretory cells does not result from impaired proliferation of progenitor cells induced by Cdkn2a activation but rather from direct regulation of transcription factors responsible for secretory lineage commitment. Overall, our data uncover a dual role of PRC 2 in intestinal homeostasis highlighting the importance of this repressive layer in controlling cell plasticity and lineage choices in adult tissues.