TY - JOUR
T1 - Polycomb Complex PRC1 Preserves Intestinal Stem Cell Identity by Sustaining Wnt/β-Catenin Transcriptional Activity
AU - Chiacchiera, Fulvio
AU - Rossi, Alessandra
AU - Jammula, Sriganesh
AU - Piunti, Andrea
AU - Scelfo, Andrea
AU - Ordóñez-Morán, Paloma
AU - Huelsken, Joerg
AU - Koseki, Haruhiko
AU - Pasini, Diego
PY - 2016/1/7
Y1 - 2016/1/7
N2 - Polycomb repressive complexes (PRCs) are among the most important gatekeepers of establishing and maintaining cell identity in metazoans. PRC1, which plays a dominant role in this context, executes its functions via multiple subcomplexes, which all contribute to H2AK119 mono-ubiquitination (H2Aubq). Despite our comprehensive knowledge of PRC1-dependent H2Aubq in embryonic stem cells and during early development, its role in adult stem cells still remains poorly characterized. Here we show that PRC1 activity is required for the integrity of the intestinal epithelium, regulating stem cell self-renewal via a cell-autonomous mechanism that is independent from Cdkn2a expression. By dissecting the PRC1-dependent transcription program in intestinal stem cells, we demonstrate that PRC1 represses a large number of non-lineage-specific transcription factors that directly affect β-catenin/Tcf transcriptional activity. Our data reveal that PRC1 preserves Wnt/β-catenin activity in adult stem cells to maintain intestinal homeostasis and supports tumor formation induced by the constitutive activation of this pathway.
AB - Polycomb repressive complexes (PRCs) are among the most important gatekeepers of establishing and maintaining cell identity in metazoans. PRC1, which plays a dominant role in this context, executes its functions via multiple subcomplexes, which all contribute to H2AK119 mono-ubiquitination (H2Aubq). Despite our comprehensive knowledge of PRC1-dependent H2Aubq in embryonic stem cells and during early development, its role in adult stem cells still remains poorly characterized. Here we show that PRC1 activity is required for the integrity of the intestinal epithelium, regulating stem cell self-renewal via a cell-autonomous mechanism that is independent from Cdkn2a expression. By dissecting the PRC1-dependent transcription program in intestinal stem cells, we demonstrate that PRC1 represses a large number of non-lineage-specific transcription factors that directly affect β-catenin/Tcf transcriptional activity. Our data reveal that PRC1 preserves Wnt/β-catenin activity in adult stem cells to maintain intestinal homeostasis and supports tumor formation induced by the constitutive activation of this pathway.
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U2 - 10.1016/j.stem.2015.09.019
DO - 10.1016/j.stem.2015.09.019
M3 - Article
AN - SCOPUS:84954380059
VL - 18
SP - 91
EP - 103
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 1
ER -