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

Ines Schoberleitner; Ingo Bauer; Anming Huang; Evgeniya N. Andreyeva; Johanna Sebald; Katharina Pascher; Dietmar Rieder; Melanie Brunner; Valerie Podhraski; Gregor Oemer; Daniel Cázarez-García; Leila Rieder; Markus A. Keller; Robert Winkler; Dmitry V. Fyodorov; Alexandra Lusser

doi:10.1016/j.celrep.2021.109769

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

Ines Schoberleitner, Ingo Bauer, Anming Huang, Evgeniya N. Andreyeva, Johanna Sebald, Katharina Pascher, Dietmar Rieder, Melanie Brunner, Valerie Podhraski, Gregor Oemer, Daniel Cázarez-García, Leila Rieder, Markus A. Keller, Robert Winkler, Dmitry V. Fyodorov, Alexandra Lusser

Cell Biology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	109769
Journal	Cell Reports
Volume	37
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2021.109769
State	Published - Oct 5 2021

Keywords

aging
calorie restriction
chronic inflammation
epigenetics
feeding behavior
heterochromatin
histone chaperone
longevity
metabolic disease
metabolome
quantitative proteomics

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2021.109769

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Schoberleitner, I., Bauer, I., Huang, A., Andreyeva, E. N., Sebald, J., Pascher, K., Rieder, D., Brunner, M., Podhraski, V., Oemer, G., Cázarez-García, D., Rieder, L., Keller, M. A., Winkler, R., Fyodorov, D. V., & Lusser, A. (2021). CHD1 controls H3.3 incorporation in adult brain chromatin to maintain metabolic homeostasis and normal lifespan. Cell Reports, 37(1), Article 109769. https://doi.org/10.1016/j.celrep.2021.109769

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 & Lusser, A 2021, 'CHD1 controls H3.3 incorporation in adult brain chromatin to maintain metabolic homeostasis and normal lifespan', Cell Reports, vol. 37, no. 1, 109769. https://doi.org/10.1016/j.celrep.2021.109769

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

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.",

keywords = "aging, calorie restriction, chronic inflammation, epigenetics, feeding behavior, heterochromatin, histone chaperone, longevity, metabolic disease, metabolome, quantitative proteomics",

author = "Ines Schoberleitner and Ingo Bauer and Anming Huang and Andreyeva, {Evgeniya N.} and Johanna Sebald and Katharina Pascher and Dietmar Rieder and Melanie Brunner and Valerie Podhraski and Gregor Oemer and Daniel C{\'a}zarez-Garc{\'i}a and Leila Rieder and Keller, {Markus A.} and Robert Winkler and Fyodorov, {Dmitry V.} and Alexandra Lusser",

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doi = "10.1016/j.celrep.2021.109769",

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T1 - CHD1 controls H3.3 incorporation in adult brain chromatin to maintain metabolic homeostasis and normal lifespan

AU - Schoberleitner, Ines

AU - Bauer, Ingo

AU - Huang, Anming

AU - Andreyeva, Evgeniya N.

AU - Sebald, Johanna

AU - Pascher, Katharina

AU - Rieder, Dietmar

AU - Brunner, Melanie

AU - Podhraski, Valerie

AU - Oemer, Gregor

AU - Cázarez-García, Daniel

AU - Rieder, Leila

AU - Keller, Markus A.

AU - Winkler, Robert

AU - Fyodorov, Dmitry V.

AU - Lusser, Alexandra

PY - 2021/10/5

Y1 - 2021/10/5

N2 - 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.

AB - 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.

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KW - calorie restriction

KW - chronic inflammation

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KW - feeding behavior

KW - heterochromatin

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KW - metabolome

KW - quantitative proteomics

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

Abstract

Keywords

ASJC Scopus subject areas

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