CHD8

This gene encodes a member of the chromodomain-helicase-DNA binding protein family, which is characterized by a SNF2-like domain and two chromatin organization modifier domains. The encoded protein also contains brahma and kismet domains, which are common to the subfamily of chromodomain-helicase-DNA binding proteins to which this protein belongs. This gene has been shown to function in several processes that include transcriptional regulation, epigenetic remodeling, promotion of cell proliferation, and regulation of RNA synthesis. Allelic variants of this gene are associated with autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

Full Name

Chromodomain Helicase DNA Binding Protein 8

Function

DNA helicase that acts as a chromatin remodeling factor and regulates transcription. Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription.

Biological Process

ATP-dependent chromatin remodeling Source: UniProtKB
Brain development Source: GO_Central
Digestive tract development Source: GO_Central
In utero embryonic development Source: Ensembl
Negative regulation of canonical Wnt signaling pathway Source: UniProtKB
Negative regulation of fibroblast apoptotic process Source: Ensembl
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: GO_Central
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of transcription by RNA polymerase III Source: UniProtKB
Prepulse inhibition Source: Ensembl
Social behavior Source: Ensembl
Wnt signaling pathway Source: UniProtKB-KW

Cellular Location

Nucleus. Localizes to the promoter regions of several CTNNB1-responsive genes. Also present at known CTCF target sites.

Involvement in disease

Autism 18 (AUTS18): A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.

PTM

Sumoylated.