CHD8

Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.^[5][6]

CHD8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CKA, 2DL6
Identifiers
Aliases	CHD8, AUTS18, HELSNF1, chromodomain helicase DNA binding protein 8, IDDAM
External IDs	OMIM: 610528; MGI: 1915022; HomoloGene: 72405; GeneCards: CHD8; OMA:CHD8 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q11.2 Start 21,385,194 bp[1] End 21,456,126 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 C2 Start 52,435,608 bp[2] End 52,495,237 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve ventricular zone right hemisphere of cerebellum granulocyte ganglionic eminence skin of leg skin of abdomen epithelium of colon anterior pituitary spleen Top expressed in tail of embryo genital tubercle Rostral migratory stream zygote internal carotid artery ventricular zone secondary oocyte external carotid artery fossa Ileal epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding nucleotide binding ATP-dependent activity, acting on DNA helicase activity chromatin binding methylated histone binding hydrolase activity, acting on acid anhydrides DNA helicase activity protein binding hydrolase activity ATP binding p53 binding beta-catenin binding histone binding armadillo repeat domain binding Cellular component nucleoplasm MLL1 complex nucleus protein-containing complex Biological process regulation of transcription, DNA-templated negative regulation of transcription by RNA polymerase II Wnt signaling pathway transcription, DNA-templated positive regulation of transcription, DNA-templated brain development digestive tract development positive regulation of transcription by RNA polymerase III negative regulation of canonical Wnt signaling pathway positive regulation of transcription by RNA polymerase II DNA duplex unwinding chromatin organization negative regulation of Wnt signaling pathway negative regulation of transcription, DNA-templated canonical Wnt signaling pathway negative regulation of apoptotic process in utero embryonic development startle response social behavior prepulse inhibition negative regulation of fibroblast apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57680 67772 Ensembl ENSG00000100888 ENSMUSG00000053754 UniProt Q9HCK8 Q09XV5 RefSeq (mRNA) NM_020920 NM_001170629 NM_001010928 NM_201637 RefSeq (protein) NP_001164100 NP_065971 NP_963999 Location (UCSC) Chr 14: 21.39 – 21.46 Mb Chr 14: 52.44 – 52.5 Mb PubMed search [3] [4]
Wikidata
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Function

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]

Clinical significance

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^[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]