Correction to: Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life

Jiménez, Jessica A.; Ptacek, Travis; Tuttle, Alex H.; Schmid, Ralf S.; Moy, Sheryl S.; Simon, Jeremy M.; Zylka, Mark J.

doi:10.1186/s13229-021-00438-6

Cited by 2 publications

(1 citation statement)

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“…The chromatin remodeling factor CHD8 is associated with developmental brain disorders, but its molecular function in mature human neurons is largely unknown 58 . To fill this knowledge gap, we report that CHD8 is responsible for maintaining an open chromatin configuration in promoters and overall transcriptional activation in human neurons.…”

Section: Discussionmentioning

confidence: 99%

The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1

Derafshi

Dankó

Chanda

et al. 2022

Sci Rep

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The chromodomain helicase DNA-binding protein CHD8 is the most frequently mutated gene in autism spectrum disorder. Despite its prominent disease involvement, little is known about its molecular function in the human brain. CHD8 is a chromatin regulator which binds to the promoters of actively transcribed genes through genomic targeting mechanisms which have yet to be fully defined. By generating a conditional loss-of-function and an endogenously tagged allele in human pluripotent stem cells, we investigated the molecular function and the interaction of CHD8 with chromatin in human neurons. Chromatin accessibility analysis and transcriptional profiling revealed that CHD8 functions as a transcriptional activator at its target genes in human neurons. Furthermore, we found that CHD8 chromatin targeting is cell context-dependent. In human neurons, CHD8 preferentially binds at ETS motif-enriched promoters. This enrichment is particularly prominent on the promoters of genes whose expression significantly changes upon the loss of CHD8. Indeed, among the ETS transcription factors, we identified ELK1 as being most highly correlated with CHD8 expression in primary human fetal and adult cortical neurons and most highly expressed in our stem cell-derived neurons. Remarkably, ELK1 was necessary to recruit CHD8 specifically to ETS motif-containing sites. These findings imply that ELK1 and CHD8 functionally cooperate to regulate gene expression and chromatin states at MAPK/ERK target genes in human neurons. Our results suggest that the MAPK/ERK/ELK1 axis potentially contributes to the pathogenesis caused by CHD8 mutations in human neurodevelopmental disorders.

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Section: Discussionmentioning

confidence: 99%

The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1

Derafshi

Dankó

Chanda

et al. 2022

Sci Rep

View full text Add to dashboard Cite

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The complex etiology of autism spectrum disorder due to missense mutations of CHD8

Shiraishi,

Katayama,

Nishiyama

et al. 2024

Mol Psychiatry

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Correction to: Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life

Abstract: An amendment to this paper has been published and can be accessed via the original article.

Cited by 2 publications

References 1 publication

The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1

The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1

The complex etiology of autism spectrum disorder due to missense mutations of CHD8

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