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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.

SUBMITTER: Schoberleitner I

PROVIDER: S-EPMC8607513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Chd1 chromatin remodelers maintain nucleosome organization and repress cryptic transcription.

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Isw1 and Chd1 maintain chromatin organization during transcription

Project description:ChIP-chip assays to determine the localization of 3xFLAG tagged Ioc4, Ioc3 & Isw1 in wildtype and set2 yeast. Two color experiment. ChIP/Input. Biological replicates=3.

2012-07-24 | E-GEOD-32042 | biostudies-arrayexpress

Isw1 and Chd1 maintain chromatin organization during transcription [isw1 chd1 mutant expression]

Project description:Gene expression microarray experiments to determine the existence of intragenic (cryptic) transcripts in an isw1 chd1 mutant yeast strain. Two color experiment. Mutant/WT. Biological replicates=3. Hybridisation of same samples to strand-specific gene expression arrays.

2012-07-24 | E-GEOD-37158 | biostudies-arrayexpress

Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs.

Project description:Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive. Here, we study the importance of the histone variant H3.3 in Caenorhabditis elegans longevity pathways. We show that H3.3-deficient nematodes have negligible lifespan differences compared to wild-type animals. However, H3.3 is essential for the lifespan extension of C. elegans mutants in which pronounced transcriptional changes control longevity programs. Notably, H3.3 loss critically affects the expression of a very large number of genes in long-lived nematodes, resulting in transcriptional profiles similar to wild-type animals. We conclude that H3.3 positively contributes to diverse lifespan-extending signaling pathways, with potential implications on age-related processes in multicellular organisms.

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CHD1 Regulates Deposition of Histone Variant H3.3 During Bovine Early Embryonic Development.

Project description:The CHD family of proteins is characterized by the presence of chromodomains and SNF2-related helicase/ATPase domains, which alter gene expression by modification of chromatin structure. Chd1-null embryos arrest at the peri-implantation stage in mice. However, the functional role of CHD1 during preimplantation development remains unclear, given maternal-derived CHD1 may mask the essential role of CHD1 during this stage in traditional knockout models. The objective of this study was to characterize CHD1 expression and elucidate its functional role in preimplantation development using the bovine model. CHD1 mRNA was elevated after meiotic maturation and remained increased through the 16-cell stage, followed by a sharp decrease at morula to blastocyst stage. Similarly, immunoblot analysis indicated CHD1 protein level is increased after maturation, maintained at high level after fertilization and declined sharply afterwards. CHD1 mRNA level was partially decreased in response to alpha-amanitin (RNA polymerase II inhibitor) treatment, suggesting that CHD1 mRNA in eight-cell embryos is of both maternal and zygotic origin. Results of siRNA-mediated silencing of CHD1 in bovine early embryos demonstrated that the percentages of embryos developing to the 8- to 16-cell and blastocyst stages were both significantly reduced. However, expression of NANOG (inner cell mass marker) and CDX2 (trophectoderm marker) were not affected in CHD1 knockdown blastocysts. In addition, we found that histone variant H3.3 immunostaining is altered in CHD1 knockdown embryos. Knockdown of H3.3 using siRNA resulted in a similar phenotype to CHD1-ablated embryos. Collectively, our results demonstrate that CHD1 is required for bovine early development, and suggest that CHD1 may regulate H3.3 deposition during this period.

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