SUMOylation of linker histone H1 drives chromatin condensation and restriction of embryonic cell fate identity.

Animals Blastocyst / cytology Cell Lineage Chromatin / genetics Chromatin Assembly and Disassembly Embryo Culture Techniques Embryonic Development Gene Expression Regulation, Developmental HEK293 Cells Histones / genetics Humans Mice Mouse Embryonic Stem Cells / metabolism Phenotype Small Ubiquitin-Related Modifier Proteins / genetics Sumoylation Ubiquitins / genetics

Journal

Molecular cell

ISSN: 1097-4164

Titre abrégé: Mol Cell

Pays: United States

ID NLM: 9802571

Informations de publication

Date de publication:
06 01 2022

Historique:

received: 18 01 2021

revised: 08 11 2021

accepted: 10 11 2021

pubmed: 8 12 2021

medline: 15 2 2022

entrez: 7 12 2021

Statut: ppublish

Résumé

The fidelity of the early embryonic program is underlined by tight regulation of the chromatin. Yet, how the chromatin is organized to prohibit the reversal of the developmental program remains unclear. Specifically, the totipotency-to-pluripotency transition marks one of the most dramatic events to the chromatin, and yet, the nature of histone alterations underlying this process is incompletely characterized. Here, we show that linker histone H1 is post-translationally modulated by SUMO2/3, which facilitates its fixation onto ultra-condensed heterochromatin in embryonic stem cells (ESCs). Upon SUMOylation depletion, the chromatin becomes de-compacted and H1 is evicted, leading to totipotency reactivation. Furthermore, we show that H1 and SUMO2/3 jointly mediate the repression of totipotent elements. Lastly, we demonstrate that preventing SUMOylation on H1 abrogates its ability to repress the totipotency program in ESCs. Collectively, our findings unravel a critical role for SUMOylation of H1 in facilitating chromatin repression and desolation of the totipotent identity.

Identifiants

DOI: 10.1016/j.molcel.2021.11.011 PMID: 34875212

pubmed: 34875212

pii: S1097-2765(21)00990-4

doi: 10.1016/j.molcel.2021.11.011

pii:

doi:

Substances chimiques

Chromatin 0

Histones 0

SUMO2 protein, mouse 0

Small Ubiquitin-Related Modifier Proteins 0

Sumo3 protein, mouse 0

Ubiquitins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

106-122.e9

Subventions

Organisme : NIGMS NIH HHS

ID : R35 GM138386

Pays : United States

Informations de copyright

Déclaration de conflit d'intérêts

Declarations of interests The authors declare no competing interests.