The acetyltransferase KAT7 is required for thymic epithelial cell expansion, expression of AIRE target genes, and thymic tolerance.

Animals Epithelial Cells / immunology Histone Acetyltransferases / immunology Immune Tolerance / immunology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Thymus Gland / cytology Transcription Factors / immunology AIRE Protein

Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
21 01 2022
Historique:
entrez: 21 1 2022
pubmed: 22 1 2022
medline: 9 3 2022
Statut: ppublish

Résumé

The autoimmune regulator (AIRE) induces the transcription of thousands of peripheral tissue genes (PTGs) in thymic epithelial cells (TECs) to mediate immunological tolerance. The chromatin state required for optimal AIRE function in TECs and how this state is induced remains unclear. We tested the role of the histone acetyltransferase, KAT7 (also known as HBO1 or MYST2), which is essential for acetylation of histone 3 lysine 14, in TEC differentiation, AIRE-mediated PTG expression, and thymic tolerance. We find that KAT7 is required for optimal expansion of medullary TEC and has a major role in the expression of AIRE-dependent PTGs, associated with enhanced chromatin accessibility at these gene loci in TECs. Mice with TEC-specific

Identifiants

DOI: 10.1126/sciimmunol.abb6032 PMID: 35061506
pubmed: 35061506
doi: 10.1126/sciimmunol.abb6032
doi:

Substances chimiques

Transcription Factors 0
Histone Acetyltransferases EC 2.3.1.48
Kat7 protein, mouse EC 2.3.1.48

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabb6032

Auteurs

Melanie Heinlein (M)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
ORCID: 0000-0001-6194-7159

Luke C Gandolfo (LC)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3052, Australia.
ORCID: 0000-0002-3599-2455

Kelin Zhao (K)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
ORCID: 0000-0002-2817-0445

Charis E Teh (CE)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
ORCID: 0000-0002-9745-2876

Nghi Nguyen (N)

Medicinal Chemistry Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
ORCID: 0000-0001-7496-7300

Jonathan B Baell (JB)

Medicinal Chemistry Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
ORCID: 0000-0003-2114-8242

Yael Goldfarb (Y)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
ORCID: 0000-0002-9472-9577

Jakub Abramson (J)

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Johannes Wichmann (J)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.

Anne K Voss (AK)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.

Andreas Strasser (A)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.

Gordon K Smyth (GK)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3052, Australia.
ORCID: 0000-0001-9221-2892

Tim Thomas (T)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.

Daniel H D Gray (DHD)

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
ORCID: 0000-0002-8457-8242

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Cellules › Cellules épithéliales › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Acyltransferases › Acetyltransferases › Lysine acetyltransferases › Histone acetyltransferases › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunomodulation › Tolérance immunitaire › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système lymphatique › Tissu lymphoïde › Thymus (glande) › The acetyltransferase KAT7 is required for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › The acetyltransferase KAT7 is required for...