Autism-associated chromatin remodeler CHD8 regulates erythroblast cytokinesis and fine-tunes the balance of Rho GTPase signaling

Tu, Zhaowei; Fan, Cuiqing; Davis, Ashely K; Hu, Mei‐Chen; Wang, Chen; Dandamudi, Akhila; Seu, Katie Giger; Kalfa, Theodosia A.; Lü, Qing; Zheng, Yi

doi:10.1016/j.celrep.2022.111072

Cited by 2 publications

(1 citation statement)

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“…Previous studies on Chd8 -mutant mice and human neurons suggested multiple mechanisms that may underlie CHD8-related brain deficits ( Sugathan et al, 2014 ; Cotney et al, 2015 ; Wang et al, 2015 ; Breuss and Gleeson, 2016 ; Durak et al, 2016 ; Katayama et al, 2016 ; Gompers et al, 2017 ; Platt et al, 2017 ; Wang et al, 2017 ; Andreae and Basson, 2018 ; Jung et al, 2018 ; Suetterlin et al, 2018 ; Wade et al, 2018 ; Xu et al, 2018 ; Zhao et al, 2018 ; Hulbert et al, 2020 ; Jimenez et al, 2020 ; Sood et al, 2020 ; Cherepanov et al, 2021 ; Ding et al, 2021 ; Ellingford et al, 2021 ; Hurley et al, 2021 ; Kawamura et al, 2021 ; Kweon et al, 2021 ; Weissberg and Elliott, 2021 ; Chen et al, 2022 ; Coakley-Youngs et al, 2022 ; Dong et al, 2022 ; Haddad Derafshi et al, 2022 ; Jimenez et al, 2022 ; Kerschbamer et al, 2022 ; Lee et al, 2022 ; Paulsen et al, 2022 ; Thudium et al, 2022 ; Tu et al, 2022 ; Villa et al, 2022 ; Yu et al, 2022 ; Hayot et al, 2023 ). However, mechanisms underlying the male–female differences in CHD8-related ASD are poorly understood ( Jung et al, 2018 ; Cherepanov et al, 2021 ; Yu et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

Lee

Kweon²,

Kang³

et al. 2023

Front. Mol. Neurosci.

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Chd8+/N2373K mice with a human C-terminal-truncating mutation (N2373K) display autistic-like behaviors in juvenile and adult males but not in females. In contrast, Chd8+/S62X mice with a human N-terminal-truncating mutation (S62X) display behavioral deficits in juvenile males (not females) and adult males and females, indicative of age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8+/S62X juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8+/S62X males but in newborn and adult (not juvenile) Chd8+/S62X females. These results point to age-differential sexual dimorphisms in Chd8+/S62X mice at synaptic and transcriptomic levels, in addition to the behavioral level.

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Section: Introductionmentioning

confidence: 99%

Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

Lee

Kweon²,

Kang³

et al. 2023

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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Autism-associated chromatin remodeler CHD8 regulates erythroblast cytokinesis and fine-tunes the balance of Rho GTPase signaling

Cited by 2 publications

References 43 publications

Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

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

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