Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility.

Animals Cell Differentiation / physiology Chromatin / metabolism Epigenomics Interferon-gamma / genetics Mice Multiple Sclerosis / genetics Myelin Sheath / metabolism Oligodendroglia / metabolism
Polycomb chromatin genome-wide association studies histone modifications major histocompatibility complex multiple sclerosis myelin neuroimmunology oligodendrocyte single-nucleotide polymorphisms

Journal

Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320

Informations de publication

Date de publication:
06 04 2022
Historique:
received: 14 01 2021
revised: 05 11 2021
accepted: 27 12 2021
pubmed: 31 1 2022
medline: 12 4 2022
entrez: 30 1 2022
Statut: ppublish

Résumé

Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG) and myelin by immune cells, which are thought to be the main drivers of MS susceptibility. We found that immune genes exhibit a primed chromatin state in single mouse and human OLG in a non-disease context, compatible with transitions to immune-competent states in MS. We identified BACH1 and STAT1 as transcription factors involved in immune gene regulation in oligodendrocyte precursor cells (OPCs). A subset of immune genes presents bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon gamma (IFN-γ) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse and human OLG. Treatment of mouse OPCs with IFN-γ leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Thus, the susceptibility for MS may involve OLG, which therefore constitutes novel targets for immunological-based therapies for MS.

Identifiants

DOI: 10.1016/j.neuron.2021.12.034 PMID: 35093191 PMC: PMC9810341
pubmed: 35093191
pii: S0896-6273(21)01089-8
doi: 10.1016/j.neuron.2021.12.034
pmc: PMC9810341
mid: NIHMS1854707
pii:
doi:

Substances chimiques

Chromatin 0
Interferon-gamma 82115-62-6

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1193-1210.e13

Subventions

Organisme : NHGRI NIH HHS
ID : RM1 HG007735
Pays : United States
Organisme : NIA NIH HHS
ID : K99 AG059918
Pays : United States
Organisme : Medical Research Council
ID : MR/S02638X/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : P50 NS062684
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG072573
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG059918
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Department of Health
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests H.Y.C. is a co-founder of Accent Therapeutics and Boundless Bio and an advisor to 10x Genomics, Arsenal Biosciences, and Spring Discovery. D.M. and D.C. are employees at Roche Pharma Research and Early Development. The other authors declare no competing interests.

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Auteurs

Mandy Meijer (M)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Eneritz Agirre (E)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Mukund Kabbe (M)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Cassandra A van Tuijn (CA)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Abeer Heskol (A)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden; Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.

Chao Zheng (C)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Ana Mendanha Falcão (A)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's Associate Laboratory, PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal.

Marek Bartosovic (M)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Leslie Kirby (L)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Daniela Calini (D)

Roche Pharma Research and Early Development, 4070 Basel, Switzerland.

Michael R Johnson (MR)

Faculty of Medicine, Department of Brain Sciences, Imperial College of London, SW7 2AZ London, UK.

M Ryan Corces (MR)

Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA; Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

Thomas J Montine (TJ)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

Xingqi Chen (X)

Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA; Department of Immunology, Genetics, and Pathology, Uppsala University, 751 85 Uppsala, Sweden.

Howard Y Chang (HY)

Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305-5101, USA.

Dheeraj Malhotra (D)

Roche Pharma Research and Early Development, 4070 Basel, Switzerland.

Gonçalo Castelo-Branco (G)

Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden; Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address: goncalo.castelo-branco@ki.se.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Lymphokines › Facteurs d'activation des macrophages › Interféron gamma › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Cellules › Neurones › Neurofibres › Gaine de myéline › Epigenomic priming of immune genes implicates...
questionsmedicales.fr › Cellules › Névroglie › Oligodendroglie › Epigenomic priming of immune genes implicates...