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PMID: 20064376 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells.

Cell ·Vol. 139 ·No. 7 ·2009-12-24 ·Pages 1303-14

Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan GC, Lee Y, Orkin SH

Abstract

Trimethylation on histone H3 lysine 27 (H3K27me3) by Polycomb repressive complex 2 (PRC2) regulates the balance between self-renewal and differentiation of embryonic stem cells (ESCs). The mechanisms controlling the activity and recruitment of PRC2 are largely unknown. Here we demonstrate that the founding member of the Jumonji family, JMJ (JUMONJI or JARID2), is associated with PRC2, colocalizes with PRC2 and H3K27me3 on chromatin, and modulates PRC2 function. In vitro JMJ inhibits PRC2 methyltransferase activity, consistent with increased H3K27me3 marks at PRC2 targets in Jmj(-/-) ESCs. Paradoxically, JMJ is required for efficient binding of PRC2, indicating that the interplay of PRC2 and JMJ fine-tunes deposition of the H3K27me3 mark. During differentiation, activation of genes marked by H3K27me3 and lineage commitments are delayed in Jmj(-/-) ESCs. Our results demonstrate that dynamic regulation of Polycomb complex activity orchestrated by JMJ balances self-renewal and differentiation, highlighting the involvement of chromatin dynamics in cell-fate transitions.

MeSH Terms
Animals Cell Differentiation Chromatin Assembly and Disassembly Embryonic Stem Cells/cytology HeLa Cells Histone-Lysine N-Methyltransferase/metabolism Histones/metabolism Humans Mice Nerve Tissue Proteins/metabolism Polycomb Repressive Complex 2 Polycomb-Group Proteins Repressor Proteins/metabolism
Chemicals
Histones Jarid2 protein, mouse Nerve Tissue Proteins Polycomb-Group Proteins Repressor Proteins Histone-Lysine N-Methyltransferase Polycomb Repressive Complex 2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Shen Xiaohua
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Kim Woojin
Fujiwara Yuko
Simon Matthew D
Liu Yingchun
Mysliwiec Matthew R
Yuan Guo-Cheng
Lee Youngsook
Orkin Stuart H
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.12.003
Published
2009-12-24
Pages
1303-14
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2810107
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · P30 DK049216 · United States
NIDDK NIH HHS · P30 DK049216-16 · United States
NHLBI NIH HHS · HL67050 · United States
Databases
GEO
GSE19169
External Links
PubMed source DOI: 10.1016/j.cell.2009.12.003 PMC Full Text View journal details
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