BRD9-containing non-canonical BAF complex maintains somatic cell transcriptome and acts as a barrier to human reprogramming.

Autor:	Sevinç K; School of Medicine, Koç University, Istanbul, Turkey., Sevinç GG; School of Medicine, Koç University, Istanbul, Turkey., Cavga AD; School of Medicine, Koç University, Istanbul, Turkey; Biostatistics, Bioinformatics and Data Management Core, KUTTAM, Koç University, Istanbul, Turkey., Philpott M; Botnar Research Centre, Oxford NIHR BRU, University of Oxford, Oxford, UK., Kelekçi S; School of Medicine, Koç University, Istanbul, Turkey., Can H; School of Medicine, Koç University, Istanbul, Turkey., Cribbs AP; Botnar Research Centre, Oxford NIHR BRU, University of Oxford, Oxford, UK., Yıldız AB; School of Medicine, Koç University, Istanbul, Turkey., Yılmaz A; School of Medicine, Koç University, Istanbul, Turkey., Ayar ES; School of Medicine, Koç University, Istanbul, Turkey., Arabacı DH; School of Medicine, Koç University, Istanbul, Turkey., Dunford JE; Botnar Research Centre, Oxford NIHR BRU, University of Oxford, Oxford, UK., Ata D; School of Medicine, Koç University, Istanbul, Turkey., Sigua LH; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, USA., Qi J; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA, USA., Oppermann U; Botnar Research Centre, Oxford NIHR BRU, University of Oxford, Oxford, UK; Centre for Medicine Discovery, University of Oxford, Oxford, UK; Oxford Centre for Translational Myeloma Research, University of Oxford, Oxford OX3 7LD, UK., Onder TT; School of Medicine, Koç University, Istanbul, Turkey. Electronic address: tonder@ku.edu.tr.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2022 Dec 13; Vol. 17 (12), pp. 2629-2642. Date of Electronic Publication: 2022 Nov 03.
DOI:	10.1016/j.stemcr.2022.10.005
Abstrakt:	Epigenetic reprogramming to pluripotency requires extensive remodeling of chromatin landscapes to silence existing cell-type-specific genes and activate pluripotency genes. ATP-dependent chromatin remodeling complexes are important regulators of chromatin structure and gene expression; however, the role of recently identified Bromodomain-containing protein 9 (BRD9) and the associated non-canonical BRG1-associated factors (ncBAF) complex in reprogramming remains unknown. Here, we show that genetic or chemical inhibition of BRD9, as well as ncBAF complex subunit GLTSCR1, but not the closely related BRD7, increase human somatic cell reprogramming efficiency and can replace KLF4 and c-MYC. We find that BRD9 is dispensable for human induced pluripotent stem cells under primed but not under naive conditions. Mechanistically, BRD9 inhibition downregulates fibroblast-related genes and decreases chromatin accessibility at somatic enhancers. BRD9 maintains the expression of transcriptional regulators MN1 and ZBTB38, both of which impede reprogramming. Collectively, these results establish BRD9 as an important safeguarding factor for somatic cell identity whose inhibition lowers chromatin-based barriers to reprogramming. Competing Interests: CONFLICT OF INTERESTS The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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