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

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

doi:10.1016/j.celrep.2021.109769

Cited by 11 publications

(19 citation statements)

References 102 publications

(138 reference statements)

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“…For instance, rhodopsin genes, genes encoding Obp and defective proboscis extension response ( dpr ) genes as well as genes encoding N-methyl-D-aspartate (NMDA) receptors were significantly upregulated in Chd1 –/– flies compared to Chd1 WT/WT or Chd1 elav ( Figures 1B–D ). Furthermore, many G-protein coupled signaling-linked genes had increased transcription in Chd1 –/– compared to Chd1 WT/WT or Chd1 elav heads ( Figure 1E ; Schoberleitner et al, 2021 ). These included genes related to serotonin-, dopamine-, GABA-, or octopaminergic signaling, along with allostatic, acetylcholine, rhodopsin, and tachykinin associated signaling ( Figure 1E ).…”

Section: Resultsmentioning

confidence: 99%

“…To examine if and how CHD1 might affect sensory perception in Drosophila , we turned to our previously generated RNA-seq data from fly heads ( Schoberleitner et al, 2021 ). The data set contains gene expression profiles from Chd1 -deletion mutant flies (termed Chd1 –/– ), from Chd1 -deletion mutant flies rescued by transgenic expression of Chd1 under the control of its native promoter (termed Chd1 WT/WT ) and from mutant flies that were rescued by neuron-specific expression of Chd1 under the control of the elav promoter (termed Chd1 elav ).…”

Section: Resultsmentioning

confidence: 99%

“…Elav-Gal4 (Stock ID 8760) line was obtained from the Bloomington Stock Center. For detailed description of strain genotypes see Schoberleitner et al (2021) .…”

Section: Methodsmentioning

confidence: 99%

“…RNA-seq data from virgin female Drosophila heads ( Schoberleitner et al, 2021 ); GEO accession number ( GSE146392 ) were subjected to gene ontology analysis using the GOrilla tool ( Eden et al, 2009 ) by comparing the unranked target list (differentially expressed genes with log2 fold change ≥1, adjusted p -value ≤ 0.05 and base mean ≥20) with a background list containing all transcripts identified in the sequencing analysis. Heatmaps of significantly enriched gene categories were generated using the R package pheatmap ( Kolde, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

“…Consistent with this, we found that many genes linked to the regulation of hunger and satiety were dysregulated in the heads of mutant flies. Re-expression of CHD1 only in neurons rescued all these phenotypes ( Schoberleitner et al, 2021 ) emphasizing the critical role of this chromatin assembly factor for brain function.…”

Section: Introductionmentioning

confidence: 95%

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Regulation of sensory perception and motor abilities by brain-specific action of chromatin remodeling factor CHD1

Schoberleitner

Mertens

Bauer

et al. 2022

Front. Mol. Neurosci.

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The ATP-dependent chromatin remodeling factor CHD1 (chromodomain-helicase-DNA binding protein 1) is involved in both the de novo assembly and the remodeling of chromatin. Recently, we discovered a crucial role of CHD1 in the incorporation of the histone variant H3.3 in the fly brain illustrated by widespread transcriptional upregulation and shortened lifespan in Chd1-mutant animals. Because many genes linked to sensory perception were dysregulated in Chd1-mutant heads, we studied the role of CHD1 in these processes. Here we show that Chd1-mutant flies have severe defects in their response behavior to olfactory and gustatory but not visual stimuli. Further analyses suggested that poor performance in gustatory response assays was caused by reduced motivation for foraging and feeding rather than defects in taste perception. Moreover, we show that shortened lifespan of Chd1-mutant flies is accompanied by indications of premature functional aging as suggested by defects in negative geotaxis and exploratory walking assays. The latter phenotype was rescued by neuronal re-expression of Chd1, while the olfactory defects were not. Interestingly, we found evidence for indirect regulation of the non-neuronal expression of odorant binding proteins (Obp) by neuronal expression of Chd1. Together, these results emphasize the crucial role of CHD1 activity controlling diverse neuronal processes thereby affecting healthy lifespan.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Elav-Gal4 (Stock ID 8760) line was obtained from the Bloomington Stock Center. For detailed description of strain genotypes see Schoberleitner et al (2021) .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Regulation of sensory perception and motor abilities by brain-specific action of chromatin remodeling factor CHD1

Schoberleitner

Mertens

Bauer

et al. 2022

Front. Mol. Neurosci.

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Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

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2023

Encyclopedia of Life Sciences

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Vital processes such as transcription, repair, replication and recombination continuously shape cellular chromatin landscape. The chromodomain helicase DNA‐binding (CHD) family of enzymes regulate chromatin dynamics by utilising energy from ATP hydrolysis to alter nucleosomal position, structure and composition, thereby modulating accessibility of the underlying DNA sequence. The CHD enzymes are highly conserved in evolution, and genetic studies in fungi, plants and animals demonstrate their critical roles in regulation of cellular identity and fate and organismal development. Advances in genomic studies over the past two decades led to the identification of frequent DNA copy‐number alterations, mutations and aberrant expression of CHDs in human malignancies and various disorders, highlighting their importance as relevant biomarkers or targets for therapeutic intervention. Key Concepts CHD family of enzymes (CHD1‐9) are evolutionary conserved ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes, such as transcription, replication and repair. They are critical for normal organismal development and are frequently mutated in human disorders and cancers. Chromodomain helicase DNA‐binding proteins (CHD1‐9) are evolutionary conserved family of ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes such as transcription, replication and DNA repair. CHD enzymes share a common domain structure: two N‐terminal chromodomains, a central ATPase/helicase domain, and a C‐terminal DNA‐binding domain. CHD proteins play crucial roles in diverse cellular processes, including embryonic development, stem cell maintenance and differentiation, and tissue‐specific gene expression. Dysregulation of CHD proteins has been associated with various human diseases, including cancer and neurodevelopmental disorders. CHD proteins are attractive targets for the development of new therapies for diseases associated with chromatin dysfunction. Understanding the molecular mechanisms underlying the function of CHD proteins may pave the way for the development of new drugs that target these proteins and improve the treatment of a variety of human diseases.

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H3.3B controls aortic dissection progression by regulating vascular smooth muscle cells phenotypic transition and vascular inflammation

et al. 2023

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

Cited by 11 publications

References 102 publications

Regulation of sensory perception and motor abilities by brain-specific action of chromatin remodeling factor CHD1

Regulation of sensory perception and motor abilities by brain-specific action of chromatin remodeling factor CHD1

Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

H3.3B controls aortic dissection progression by regulating vascular smooth muscle cells phenotypic transition and vascular inflammation

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