1. CHD1 controls H3.3 incorporation in adult brain chromatin to maintain metabolic homeostasis and normal lifespan.
- Author
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Schoberleitner I, Bauer I, Huang A, Andreyeva EN, Sebald J, Pascher K, Rieder D, Brunner M, Podhraski V, Oemer G, Cázarez-García D, Rieder L, Keller MA, Winkler R, Fyodorov DV, and Lusser A
- Subjects
- Animals, Animals, Genetically Modified metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Chromatin chemistry, Chromatin Assembly and Disassembly, DNA-Binding Proteins deficiency, DNA-Binding Proteins metabolism, Drosophila Proteins deficiency, Drosophila Proteins genetics, Drosophila melanogaster metabolism, Feeding Behavior, Female, Histone Chaperones genetics, Histone Chaperones metabolism, Histones analysis, Longevity, Male, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Transcription Factors deficiency, Transcription Factors metabolism, Brain metabolism, Chromatin metabolism, DNA-Binding Proteins genetics, Drosophila Proteins metabolism, Histones metabolism, Metabolome physiology, Transcription Factors genetics
- Abstract
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.)
- Published
- 2021
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