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Cell Stem Cell. 2018 Nov 1;23(5):742-757.e8. doi: 10.1016/j.stem.2018.10.001. Epub 2018 Oct 25.

SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States.

Author information

1
Nuclear Organization and Oncogenesis Unit, Equipe Labellisée Ligue Nationale Contre le Cancer, Institut Pasteur, 75015 Paris, France; INSERM, U993, 75015 Paris, France.
2
Nuclear Organization and Oncogenesis Unit, Equipe Labellisée Ligue Nationale Contre le Cancer, Institut Pasteur, 75015 Paris, France; INSERM, U993, 75015 Paris, France; Sorbonne Université, Collège Doctoral, 75005 Paris, France.
3
Bioinformatics and Biostatistics Hub - C3BI, USR 3756 Institut Pasteur & CNRS, 75015 Paris, France.
4
Cellular Plasticity and Disease Modelling Unit, Institut Pasteur, 75015 Paris, France; CNRS UMR3738, 75015 Paris, France.
5
Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, München, Germany.
6
Experimental Neuropathology Unit, Institut Pasteur, 75015 Paris, France.
7
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.
8
Nuclear Organization and Oncogenesis Unit, Equipe Labellisée Ligue Nationale Contre le Cancer, Institut Pasteur, 75015 Paris, France; INSERM, U993, 75015 Paris, France. Electronic address: anne.dejean@pasteur.fr.

Abstract

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.

KEYWORDS:

2C-like cells; Dux; SUMO; cell fate change; chromatin; embryonic stem cells; pluripotency; reprogramming; totipotency; transdifferentiation

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PMID:
30401455
DOI:
10.1016/j.stem.2018.10.001

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