Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation.

Acetylation Animals Cells, Cultured Chromatin / metabolism Drosophila Drosophila Proteins / genetics Epigenomics Female Gene Expression Profiling Histones / metabolism Male Mice Nuclear Proteins / genetics Pregnancy Promoter Regions, Genetic / genetics RNA Interference / physiology Transcriptional Activation / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 05 2020
Historique:
received: 19 09 2019
accepted: 14 04 2020
entrez: 9 5 2020
pubmed: 10 5 2020
medline: 18 8 2020
Statut: epublish

Résumé

Cells rely on a diverse repertoire of genes for maintaining homeostasis, but the transcriptional networks underlying their expression remain poorly understood. The MOF acetyltransferase-containing Non-Specific Lethal (NSL) complex is a broad transcription regulator. It is essential in Drosophila, and haploinsufficiency of the human KANSL1 subunit results in the Koolen-de Vries syndrome. Here, we perform a genome-wide RNAi screen and identify the BET protein BRD4 as an evolutionary conserved co-factor of the NSL complex. Using Drosophila and mouse embryonic stem cells, we characterise a recruitment hierarchy, where NSL-deposited histone acetylation enables BRD4 recruitment for transcription of constitutively active genes. Transcriptome analyses in Koolen-de Vries patient-derived fibroblasts reveals perturbations with a cellular homeostasis signature that are evoked by the NSL complex/BRD4 axis. We propose that BRD4 represents a conserved bridge between the NSL complex and transcription activation, and provide a new perspective in the understanding of their functions in healthy and diseased states.

Identifiants

DOI: 10.1038/s41467-020-16103-0 PMID: 32382029 PMC: PMC7206058
pubmed: 32382029
doi: 10.1038/s41467-020-16103-0
pii: 10.1038/s41467-020-16103-0
pmc: PMC7206058
doi:

Substances chimiques

Chromatin 0
Drosophila Proteins 0
Histones 0
Nuclear Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2243

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Auteurs

Aline Gaub (A)

Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany.
ORCID: 0000-0002-3571-9547

Bilal N Sheikh (BN)

Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany.
ORCID: 0000-0002-1970-6236

M Felicia Basilicata (MF)

Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany.
ORCID: 0000-0002-1111-9459

Marie Vincent (M)

CHU Nantes, Service de Génétique Médicale, 38 Boulevard Jean Monnet, 44000, Nantes, France.
ORCID: 0000-0003-1010-5618

Mathilde Nizon (M)

CHU Nantes, Service de Génétique Médicale, 38 Boulevard Jean Monnet, 44000, Nantes, France.

Cindy Colson (C)

Service Génétique, Génétique Clinique, CHU, Avenue Georges Clemenceau CS 30001, 14033, Caen, France.
Normandy University, UNICAEN, BIOTARGEN, Esplanade de la Paix CS 14032, 14032, Caen, France.

Matthew J Bird (MJ)

Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Herestraat 49, 3000, Leuven, Belgium.

James E Bradner (JE)

Novartis Institutes for Biomedical Research, 181 Massachusetts Ave, Cambridge, MA, 02139, USA.
ORCID: 0000-0002-2718-4415

Julien Thevenon (J)

CNRS UMR 5309, INSERM, U1209, Institute of Advanced Biosciences, Université Grenoble-Alpes CHU Grenoble, Allée des Alpes, 38700, La Tronche Grenoble, France.

Michael Boutros (M)

Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.
Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Asifa Akhtar (A)

Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany. akhtar@ie-freiburg.mpg.de.
ORCID: 0000-0001-8973-6193

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Classifications MeSH

questionsmedicales.fr › Métabolisme › Acylation › Acétylation › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Eucaryotes › Animaux › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Cellules › Cellules cultivées › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Pterygota › Neoptera › Holometabola › Diptera › Drosophilidae › Drosophila › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines d'arthropode › Protéines d'insecte › Protéines de Drosophila › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Interférence par ARN › Evolutionary conserved NSL complex/BRD4 axis...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Activation de la transcription › Evolutionary conserved NSL complex/BRD4 axis...