The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8,[7] which is a chromatin regulator enzyme that is essential during fetal development.[8] CHD8 is an ATP dependent enzyme.[9]
The protein contains an Snf2 helicase domain that is responsible for the hydrolysis of ATP to ADP.[9] CHD8 encodes for a DNA helicase that function as a transcription repressor by remodeling chromatin structure by altering the position of nucleosomes.[8] CHD8 negatively regulates Wnt signaling.[10] Wnt signaling is important in the vertebrate early development and morphogenesis. It is believed that CHD8 also recruits the linker histone H1 and causes the repression of β-catenin and p53 target genes.[7] The importance of CHD8 can be observed in studies where CHD8-knockout mice died after 5.5 embryonic days because of widespread p53 induced apoptosis.[7]
Recently CD8 has been associated to the regulation of long non-coding RNAs (lncRNAs),[11] and the regulation of X chromosome inactivation (XCI) initiation, via regulation of Xist long non-coding RNA, the master regulator of XCI, though competitive binding to Xist regulatory regions.[12]
Mutations in this gene have been linked to a subset of autism[13] cases in human and mouse models.[14]
Mutations in CHD8 could lead to upregulation of β-catenin-regulated genes, in some part of the brain this upregulation can cause brain overgrowth also known as macrocephaly, which occurs in 15-35% of autistic children.[8]
Some studies have determined the role of CHD8 in autism spectrum disorder (ASD).[8] CHD8 expression significantly increases during human mid-fetal development.[7] The chromatin remodeling activity and its interaction with transcriptional regulators have shown to play an important role in ASD aetiology.[15] The developing mammalian brain has a conserved CHD8 target regions that are associated with ASD risk genes.[8] The knockdown of CHD8 in human neural stem cells results in dysregulation of ASD risk genes that are targeted by CHD8.[16]
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