Phosphorylated histone variant γH2Av is associated with chromatin insulators in Drosophila.


Journal

PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074

Informations de publication

Date de publication:
10 2022
Historique:
received: 30 03 2022
accepted: 24 08 2022
revised: 17 10 2022
pubmed: 6 10 2022
medline: 20 10 2022
entrez: 5 10 2022
Statut: epublish

Résumé

Chromatin insulators are responsible for orchestrating long-range interactions between enhancers and promoters throughout the genome and align with the boundaries of Topologically Associating Domains (TADs). Here, we demonstrate an association between gypsy insulator proteins and the phosphorylated histone variant H2Av (γH2Av), normally a marker of DNA double strand breaks. Gypsy insulator components colocalize with γH2Av throughout the genome, in polytene chromosomes and in diploid cells in which Chromatin IP data shows it is enriched at TAD boundaries. Mutation of insulator components su(Hw) and Cp190 results in a significant reduction in γH2Av levels in chromatin and phosphatase inhibition strengthens the association between insulator components and γH2Av and rescues γH2Av localization in insulator mutants. We also show that γH2Av, but not H2Av, is a component of insulator bodies, which are protein condensates that form during osmotic stress. Phosphatase activity is required for insulator body dissolution after stress recovery. Together, our results implicate the H2A variant with a novel mechanism of insulator function and boundary formation.

Identifiants

pubmed: 36197938
doi: 10.1371/journal.pgen.1010396
pii: PGENETICS-D-22-00400
pmc: PMC9576066
doi:

Substances chimiques

CP190 protein, Drosophila 0
Chromatin 0
Drosophila Proteins 0
Histones 0
Microtubule-Associated Proteins 0
Nuclear Proteins 0
DNA 9007-49-2
Phosphoric Monoester Hydrolases EC 3.1.3.2

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1010396

Subventions

Organisme : NIH HHS
ID : P40 OD010949
Pays : United States
Organisme : NIH HHS
ID : P40 OD018537
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH108956
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

James R Simmons (JR)

Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, United States of America.

Ran An (R)

Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, United States of America.

Bright Amankwaa (B)

Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, United States of America.

Shannon Zayac (S)

Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, United States of America.

Justin Kemp (J)

Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, United States of America.

Mariano Labrador (M)

Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee, United States of America.

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