CHD1 controls H3.3 incorporation in adult brain chromatin to maintain metabolic homeostasis and normal lifespan.

Autor:	Schoberleitner I; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Bauer I; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Huang A; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Andreyeva EN; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Sebald J; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Pascher K; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Rieder D; Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Brunner M; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Podhraski V; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Oemer G; Institute of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria., Cázarez-García D; Department of Biotechnology and Biochemistry, Cinvestav Unidad Irapuato, Irapuato 36824, Mexico., Rieder L; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria., Keller MA; Institute of Human Genetics, Medical University of Innsbruck, Innsbruck 6020, Austria., Winkler R; Department of Biotechnology and Biochemistry, Cinvestav Unidad Irapuato, Irapuato 36824, Mexico., Fyodorov DV; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: dmitry.fyodorov@einsteinmed.org., Lusser A; Institute of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria. Electronic address: alexandra.lusser@i-med.ac.at.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Oct 05; Vol. 37 (1), pp. 109769.
DOI:	10.1016/j.celrep.2021.109769
Abstrakt:	The ATP-dependent chromatin remodeling factor CHD1 is essential for the assembly of variant histone H3.3 into paternal chromatin during sperm chromatin remodeling in fertilized eggs. It remains unclear, however, if CHD1 has a similar role in normal diploid cells. Using a specifically tailored quantitative mass spectrometry approach, we show that Chd1 disruption results in reduced H3.3 levels in heads of Chd1 mutant flies. Chd1 deletion perturbs brain chromatin structure in a similar way as H3.3 deletion and leads to global de-repression of transcription. The physiological consequences are reduced food intake, metabolic alterations, and shortened lifespan. Notably, brain-specific CHD1 expression rescues these phenotypes. We further demonstrate a strong genetic interaction between Chd1 and H3.3 chaperone Hira. Thus, our findings establish CHD1 as a factor required for the assembly of H3.3-containing chromatin in adult cells and suggest a crucial role for CHD1 in the brain as a regulator of organismal health and longevity. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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