Cover Image

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

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, an...

Full description

Saved in:
Bibliographic Details
Main Authors: Gaub, Aline (Author) , Sheikh, Bilal N. (Author) , Basilicata, M. Felicia (Author) , Vincent, Marie (Author) , Nizon, Mathilde (Author) , Colson, Cindy (Author) , Bird, Matthew J. (Author) , Bradner, James E. (Author) , Thevenon, Julien (Author) , Boutros, Michael (Author) , Akhtar, Asifa (Author)
Format: Article (Journal)
Language:English
Published: May 7, 2020
In: Nature Communications
Year: 2020, Volume: 11
ISSN:2041-1723
DOI:10.1038/s41467-020-16103-0
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-020-16103-0
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-020-16103-0
Get full text
Author Notes:Aline Gaub, Bilal N. Sheikh, M. Felicia Basilicata, Marie Vincent, Mathilde Nizon, Cindy Colson, Matthew J. Bird, James E. Bradner, Julien Thevenon, Michael Boutros & Asifa Akhtar
Description
Summary: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.
Item Description:Gesehen am 13.10.2020
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-020-16103-0

Similar Items