Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells

Semba, Yuichiro; Harada, Akihito; Maehara, Kazuhira; Oki, Shinya; Meno, Chikara; Ueda, Junji; Yamagata, Kazuya; Suzuki, Atsushi; Onimaru, Manabu; Nogami, Jumpei; Okada, Seiji; Akashi, Koichi; Ohkawa, Yasuyuki

doi:10.1093/nar/gkx475

Cited by 34 publications

(45 citation statements)

References 60 publications

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“…Broad NURF localization is consistent with the proposed model of ISWI-containing remodeling complexes continuously sampling chromatin (52). Interestingly, primary localization of NURF to the gene bodies is unique since other remodelers, including BRG1, CHD1, CHD2, CHD4, CHD7 and INO80 are primarily localized to the promoters (53)(54)(55)(56)(57). Yeast ISW1a is preferentially found at the promoters and terminators of active or repressed genes, ISW1b is located in gene bodies and at terminators of actively transcribed genes (19)(20)(21)(22)(23).…”

Section: Discussionsupporting

confidence: 80%

WITHDRAWN: The chromatin remodeling complex NURF localizes to gene bodies and is required for mRNA processing.

et al. 2018

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Section: Discussionsupporting

confidence: 80%

WITHDRAWN: The chromatin remodeling complex NURF localizes to gene bodies and is required for mRNA processing.

et al. 2018

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“…The ATP-dependent activity of CHD2 leads to assembly of chromatin into periodic nucleosome arrays by deposition of various histone proteins, thereby modifying the expression and structure of target sites (Liu et al 2015;Luijsterburg et al 2016). Functionally, CHD2 has been reported to maintain pluripotency of stem cells, influence cell fate during myogenesis and interneuron development, and facilitate DNA repair through interaction with histone variant H3.3 (Harada et al 2012;Rajagopalan et al 2012;Luijsterburg et al 2016;Meganathan et al 2017;Semba et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Autism‐linked CHD gene expression patterns during development predict multi‐organ disease phenotypes

2018

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Recent large‐scale exome sequencing studies have identified mutations in several members of the CHD (Chromodomain Helicase DNA‐binding protein) gene family in neurodevelopmental disorders. Mutations in the CHD2 gene have been linked to developmental delay, intellectual disability, autism and seizures, CHD8 mutations to autism and intellectual disability, whereas haploinsufficiency of CHD7 is associated with executive dysfunction and intellectual disability. In addition to these neurodevelopmental features, a wide range of other developmental defects are associated with mutants of these genes, especially with regards to CHD7 haploinsufficiency, which is the primary cause of CHARGE syndrome. Whilst the developmental expression of CHD7 has been reported previously, limited information on the expression of CHD2 and CHD8 during development is available. Here, we compare the expression patterns of all three genes during mouse development directly. We find high, widespread expression of these genes at early stages of development that gradually becomes restricted during later developmental stages. Chd2 and Chd8 are widely expressed in the developing central nervous system (CNS) at all stages of development, with moderate expression remaining in the neocortex, hippocampus, olfactory bulb and cerebellum of the postnatal brain. Similarly, Chd7 expression is seen throughout the CNS during late embryogenesis and early postnatal development, with strong enrichment in the cerebellum, but displays low expression in the cortex and neurogenic niches in early life. In addition to expression in the brain, novel sites of Chd2 and Chd8 expression are reported. These findings suggest additional roles for these genes in organogenesis and predict that mutation of these genes may predispose individuals to a range of other, non‐neurological developmental defects.

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“…In a murine model, CHD2 prevents suppressive chromatin formation in neurodevelopmentally regulated genes and allows the maintenance of embryonic stem cells in an undifferentiated state. It also remodels chromatin into a permissive state [34] via the replacement of histone H3 with histone H3.3 [29]. In human embryonic stem cells, CHD2 haploinsufficiency seems to impair cortical interneurons specification, which may in turn lead to the electrophysiological dysfunction of these interneurons [26].…”

Section: Resultsmentioning

confidence: 99%

Chromatin remodeling dysfunction extends the etiological spectrum of schizophrenia: a case report

et al. 2020

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Background: The role of deleterious copy number variations in schizophrenia is well established while data regarding pathogenic variations remain scarce. We report for the first time a case of schizophrenia in a child with a pathogenic mutation of the chromodomain helicase DNA binding protein 2 (CHD2) gene. Case presentation: The proband was the second child of unrelated parents. Anxiety and sleep disorders appeared at the age of 10 months. He presented febrile seizures and, at the age of 8, two generalized tonic-clonic seizures. At the age of 10, emotional withdrawal emerged, along with a flat affect, disorganization and paranoid ideation, without seizures. He began to talk and giggle with self. Eventually, the patient presented daily auditory and visual hallucinations. The diagnosis of childhood onset schizophrenia (DSM V) was then evoked. Brain imaging was unremarkable. Wakefulness electroencephalography showed a normal background and some bilateral spike-wave discharges that did not explain the psychosis features. A comparative genomic hybridization array (180 K, Agilent, Santa Clara, CA, USA) revealed an 867-kb 16p13.3 duplication, interpreted as a variant of unknown significance confirmed by a quantitative PCR that also showed its maternal inheritance. Risperidone (1,5 mg per day), led to clinical improvement. At the age of 11, an explosive relapse of epilepsy occurred with daily seizures of various types. The sequencing of a panel for monogenic epileptic disorders and Sanger sequencing revealed a de novo pathogenic heterozygous transition in CHD2 (NM_001271.3: c.4003G > T). Conclusions: This case underlines that schizophrenia may be, sometimes, underpinned by a Mendelian disease. It addresses the question of systematic genetic investigations in the presence of warning signs such as a childhood onset of the schizophrenia or a resistant epilepsy. It points that, in the absence of pathogenic copy number variation, the investigations should also include a search for pathogenic variations, which means that some of the patients with schizophrenia should benefit from Next Generation Sequencing tools. Last but not least, CHD2 encodes a member of the chromodomain helicase DNA-binding (CHD) family involved in chromatin remodeling. This observation adds schizophrenia to the phenotypic spectrum of chromodomain remodeling disorders, which may lead to innovative therapeutic approaches.

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Chd2 regulates chromatin for proper gene expression toward differentiation in mouse embryonic stem cells

Cited by 34 publications

References 60 publications

WITHDRAWN: The chromatin remodeling complex NURF localizes to gene bodies and is required for mRNA processing.

WITHDRAWN: The chromatin remodeling complex NURF localizes to gene bodies and is required for mRNA processing.

Autism‐linked CHD gene expression patterns during development predict multi‐organ disease phenotypes

Chromatin remodeling dysfunction extends the etiological spectrum of schizophrenia: a case report

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