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Protein CHD8 PDB 2dl6.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CHD8, AUTS18, HELSNF1, chromodomain helicase DNA binding protein 8
External IDs MGI: 1915022 HomoloGene: 72405 GeneCards: CHD8
RNA expression pattern
PBB GE CHD8 212571 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 14: 21.39 – 21.46 Mb Chr 14: 52.2 – 52.26 Mb
PubMed search [1] [2]
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Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.[3][4]


The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8,[5] which is a chromatin regulator enzyme that is essential during fetal development.[6] CHD8 is an ATP dependent enzyme.[7]

The protein contains an Snf2 helicase domain that is responsible for the hydrolysis of ATP to ADP.[7] CHD8 encodes for a DNA helicase that function as a transcription repressor by remodeling chromatin structure by altering the position of nucleosomes.[6] CHD8 negatively regulates Wnt signaling.[8] 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.[5] 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.[5]

Clinical significance[edit]

Mutations in this gene have been linked to a subset of autism[9] cases.

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.[6]

Some studies have determined the role of CHD8 in autism spectrum disorder (ASD).[6] CDH8 expression significantly increases during human mid-fetal development.[5] The chromatin remodeling activity and its interaction with transcriptional regulators have shown to play an important role in ASD aetiology.[10] The developing mammalian brain has a conserved CHD8 target regions that are associated with ASD risk genes.[6] The knockdown of CHD8 in human neural stem cells results in dysregulation of ASD risk genes that are targeted by CHD8.[11]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O (Aug 2000). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (4): 273–81. doi:10.1093/dnares/7.4.271. PMID 10997877. 
  4. ^ "Entrez Gene: CHD8 chromodomain helicase DNA binding protein 8". 
  5. ^ a b c d Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, Fan Y, Kikuchi A, Skoultchi AI, Nakayama KI (Feb 2009). "CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis". Nature Cell Biology. 11 (2): 172–82. doi:10.1038/ncb1831. PMC 3132516Freely accessible. PMID 19151705. 
  6. ^ a b c d e Ronan JL, Wu W, Crabtree GR (May 2013). "From neural development to cognition: unexpected roles for chromatin". Nature Reviews Genetics. 14 (5): 347–59. doi:10.1038/nrg3413. PMC 4010428Freely accessible. PMID 23568486. 
  7. ^ a b Thompson BA, Tremblay V, Lin G, Bochar DA (Jun 2008). "CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes". Molecular and Cellular Biology. 28 (12): 3894–904. doi:10.1128/MCB.00322-08. PMC 2423111Freely accessible. PMID 18378692. 
  8. ^ Nishiyama M, Skoultchi AI, Nakayama KI (Jan 2012). "Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-β-catenin signaling pathway". Molecular and Cellular Biology. 32 (2): 501–12. doi:10.1128/MCB.06409-11. PMC 3255766Freely accessible. PMID 22083958. 
  9. ^ Bernier R, Golzio C, Xiong B, Stessman HA, Coe BP, Penn O, Witherspoon K, Gerdts J, Baker C, Vulto-van Silfhout AT, Schuurs-Hoeijmakers JH, Fichera M, Bosco P, Buono S, Alberti A, Failla P, Peeters H, Steyaert J, Vissers LE, Francescatto L, Mefford HC, Rosenfeld JA, Bakken T, O'Roak BJ, Pawlus M, Moon R, Shendure J, Amaral DG, Lein E, Rankin J, Romano C, de Vries BB, Katsanis N, Eichler EE (Jul 2014). "Disruptive CHD8 mutations define a subtype of autism early in development". Cell. 158 (2): 263–76. doi:10.1016/j.cell.2014.06.017. PMC 4136921Freely accessible. PMID 24998929. 
  10. ^ Sugathan A, Biagioli M, Golzio C, Erdin S, Blumenthal I, Manavalan P, Ragavendran A, Brand H, Lucente D, Miles J, Sheridan SD, Stortchevoi A, Kellis M, Haggarty SJ, Katsanis N, Gusella JF, Talkowski ME (Oct 2014). "CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors". Proceedings of the National Academy of Sciences of the United States of America. 111 (42): E4468–77. doi:10.1073/pnas.1405266111. PMC 4210312Freely accessible. PMID 25294932. 
  11. ^ Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ, Niu W, Liu W, Klei L, Lei J, Yin J, Reilly SK, Tebbenkamp AT, Bichsel C, Pletikos M, Sestan N, Roeder K, State MW, Devlin B, Noonan JP (2015). "The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment". Nature Communications. 6 (6): 6404. doi:10.1038/ncomms7404. PMC 4355952Freely accessible. PMID 25752243. 

External links[edit]

Further reading[edit]