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Cossec, J.C.* ; Theurillat, I.* ; Chica, C.* ; Búa Aguín, S.* ; Gaume, X. ; Andrieux, A.* ; Iturbide Martinez De Albeniz, A. ; Jouvion, G.* ; Li, H.* ; Bossis, G.* ; Seeler, J.S.* ; Torres-Padilla, M.E. ; Dejean, A.*

SUMO safeguards somatic and pluripotent cell identities by enforcing distinct chromatin states.

Cell Stem Cell 23, 742-757.e8 (2018)
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Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.
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Publication type Article: Journal article
Document type Scientific Article
Keywords 2c-like Cells ; Dux ; Sumo ; Cell Fate Change ; Chromatin ; Embryonic Stem Cells ; Pluripotency ; Reprogramming ; Totipotency ; Transdifferentiation; Embryonic Stem-cells; Transcription Factors; Adipocyte Differentiation; Gene-expression; Ips Cells; Sumoylation; Methylation; Repression; Domains; Pathway
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Journal Cell Stem Cell
Quellenangaben Volume: 23, Issue: 5, Pages: 742-757.e8 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed