CHD8

2018-02-23T10:28:48Z

2601:644:400:DFBB:29A5:2869:EB87:4D3: CDH8 => CHD8 (typo)

{{Infobox_gene}}
'''Chromodomain-helicase-DNA-binding protein 8''' is an [[enzyme]] that in humans is encoded by the ''CHD8'' [[gene]].<ref name="pmid10997877">{{cite journal | vauthors = Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O | title = 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 | journal = DNA Research | volume = 7 | issue = 4 | pages = 273–81 | date = Aug 2000 | pmid = 10997877 | pmc = | doi = 10.1093/dnares/7.4.271 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CHD8 chromodomain helicase DNA binding protein 8| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57680| accessdate = }}</ref>

== Function ==

The gene CHD8 encodes the protein chromodomain helicase DNA binding protein 8,<ref name="Nature Cell">{{cite journal | vauthors = Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, Fan Y, Kikuchi A, Skoultchi AI, Nakayama KI | title = CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis | journal = Nature Cell Biology | volume = 11 | issue = 2 | pages = 172–82 | date = Feb 2009 | pmid = 19151705 | doi = 10.1038/ncb1831 | url = http://www.nature.com/ncb/journal/v11/n2/full/ncb1831.html | pmc=3132516}}</ref> which is a [[chromatin]] regulator enzyme that is essential during fetal development.<ref name="nature neural development">{{cite journal | vauthors = Ronan JL, Wu W, Crabtree GR | title = From neural development to cognition: unexpected roles for chromatin | journal = Nature Reviews Genetics | volume = 14 | issue = 5 | pages = 347–59 | date = May 2013 | pmid = 23568486 | doi = 10.1038/nrg3413 | pmc=4010428}}</ref> CHD8 is an ATP dependent enzyme.<ref name=atp>{{cite journal | vauthors = Thompson BA, Tremblay V, Lin G, Bochar DA | title = CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes | journal = Molecular and Cellular Biology | volume = 28 | issue = 12 | pages = 3894–904 | date = Jun 2008 | pmid = 18378692 | doi = 10.1128/MCB.00322-08 | pmc = 2423111 }}</ref>

The protein contains an Snf2 helicase domain that is responsible for the hydrolysis of ATP to ADP.<ref name=atp /> CHD8 encodes for a DNA helicase that function as a transcription repressor by remodeling chromatin structure by altering the position of nucleosomes.<ref name="nature neural development" /> CHD8 negatively regulates Wnt signaling.<ref name="wnt signaling">{{cite journal | vauthors = Nishiyama M, Skoultchi AI, Nakayama KI | title = Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-β-catenin signaling pathway | journal = Molecular and Cellular Biology | volume = 32 | issue = 2 | pages = 501–12 | date = Jan 2012 | pmid = 22083958 | doi = 10.1128/MCB.06409-11 | pmc=3255766}}</ref> 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.<ref name="Nature Cell" /> 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.<ref name="Nature Cell" />

== Clinical significance ==

Mutations in this gene have been linked to a subset of [[autism]]<ref>{{cite journal | vauthors = 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 | title = Disruptive CHD8 mutations define a subtype of autism early in development | journal = Cell | volume = 158 | issue = 2 | pages = 263–76 | date = Jul 2014 | pmid = 24998929 | doi = 10.1016/j.cell.2014.06.017 | pmc=4136921}}</ref> 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.<ref name="nature neural development" />

Some studies have determined the role of CHD8 in autism spectrum disorder (ASD).<ref name="nature neural development" /> CHD8 expression significantly increases during human mid-fetal development.<ref name="Nature Cell" /> The chromatin remodeling activity and its interaction with transcriptional regulators have shown to play an important role in ASD aetiology.<ref name="CHD8 Autism">{{cite journal | vauthors = 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 | title = CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 42 | pages = E4468-77 | date = Oct 2014 | pmid = 25294932 | doi = 10.1073/pnas.1405266111 | pmc=4210312}}</ref> The developing mammalian brain has a conserved CHD8 target regions that are associated with ASD risk genes.<ref name="nature neural development" /> The knockdown of CHD8 in human neural stem cells results in dysregulation of ASD risk genes that are targeted by CHD8.<ref name="autism CHD8 regulates">{{cite journal | vauthors = 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 | title = The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment | journal = Nature Communications | volume = 6 | issue = 6 | pages = 6404 | date = 2015 | pmid = 25752243 | doi = 10.1038/ncomms7404 | pmc=4355952}}</ref>

== References ==
{{reflist}}

==External links==
* {{UCSC gene info|CHD8}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T | title = Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones | journal = DNA Research | volume = 9 | issue = 3 | pages = 99–106 | date = Jun 2002 | pmid = 12168954 | doi = 10.1093/dnares/9.3.99 }}
* {{cite journal | vauthors = Epplen C, Epplen JT | title = Expression of (cac)n/(gtg)n simple repetitive sequences in mRNA of human lymphocytes | journal = Human Genetics | volume = 93 | issue = 1 | pages = 35–41 | date = Jan 1994 | pmid = 7505766 | doi = 10.1007/BF00218910 }}
* {{cite journal | vauthors = Sakamoto I, Kishida S, Fukui A, Kishida M, Yamamoto H, Hino S, Michiue T, Takada S, Asashima M, Kikuchi A | title = A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation | journal = The Journal of Biological Chemistry | volume = 275 | issue = 42 | pages = 32871–8 | date = Oct 2000 | pmid = 10921920 | doi = 10.1074/jbc.M004089200 }}
* {{cite journal | vauthors = Kobayashi M, Hanai R | title = M phase-specific association of human topoisomerase IIIbeta with chromosomes | journal = Biochemical and Biophysical Research Communications | volume = 287 | issue = 1 | pages = 282–7 | date = Sep 2001 | pmid = 11549288 | doi = 10.1006/bbrc.2001.5580 }}
* {{cite journal | vauthors = Kobayashi M, Kishida S, Fukui A, Michiue T, Miyamoto Y, Okamoto T, Yoneda Y, Asashima M, Kikuchi A | title = Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway | journal = The Journal of Biological Chemistry | volume = 277 | issue = 8 | pages = 5816–22 | date = Feb 2002 | pmid = 11744694 | doi = 10.1074/jbc.M108433200 }}
* {{cite journal | vauthors = Nishiyama M, Nakayama K, Tsunematsu R, Tsukiyama T, Kikuchi A, Nakayama KI | title = Early embryonic death in mice lacking the beta-catenin-binding protein Duplin | journal = Molecular and Cellular Biology | volume = 24 | issue = 19 | pages = 8386–94 | date = Oct 2004 | pmid = 15367660 | pmc = 516734 | doi = 10.1128/MCB.24.19.8386-8394.2004 }}
* {{cite journal | vauthors = Lin KT, Lu RM, Tarn WY | title = The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo | journal = Molecular and Cellular Biology | volume = 24 | issue = 20 | pages = 9176–85 | date = Oct 2004 | pmid = 15456888 | pmc = 517884 | doi = 10.1128/MCB.24.20.9176-9185.2004 }}
* {{cite journal | vauthors = Ishihara K, Oshimura M, Nakao M | title = CTCF-dependent chromatin insulator is linked to epigenetic remodeling | journal = Molecular Cell | volume = 23 | issue = 5 | pages = 733–42 | date = Sep 2006 | pmid = 16949368 | doi = 10.1016/j.molcel.2006.08.008 }}
* {{cite journal | vauthors = Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP | title = A probability-based approach for high-throughput protein phosphorylation analysis and site localization | journal = Nature Biotechnology | volume = 24 | issue = 10 | pages = 1285–92 | date = Oct 2006 | pmid = 16964243 | doi = 10.1038/nbt1240 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
* {{cite journal | vauthors = Yuan CC, Zhao X, Florens L, Swanson SK, Washburn MP, Hernandez N | title = CHD8 associates with human Staf and contributes to efficient U6 RNA polymerase III transcription | journal = Molecular and Cellular Biology | volume = 27 | issue = 24 | pages = 8729–38 | date = Dec 2007 | pmid = 17938208 | pmc = 2169411 | doi = 10.1128/MCB.00846-07 | last5 = Washburn | first5 = M. P. | last6 = Hernandez | first6 = N. }}
* {{cite journal | vauthors = Thompson BA, Tremblay V, Lin G, Bochar DA | title = CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes | journal = Molecular and Cellular Biology | volume = 28 | issue = 12 | pages = 3894–904 | date = Jun 2008 | pmid = 18378692 | pmc = 2423111 | doi = 10.1128/MCB.00322-08 }}
* {{cite journal | vauthors = Caldon CE, Sergio CM, Schütte J, Boersma MN, Sutherland RL, Carroll JS, Musgrove EA | title = Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc | journal = Molecular and Cellular Biology | volume = 29 | issue = 17 | pages = 4623–39 | date = Sep 2009 | pmid = 19564413 | pmc = 2725719 | doi = 10.1128/MCB.00269-09 | last5 = Sutherland | first5 = R. L. | last7 = Musgrove | last6 = Carroll | first6 = J. S. | first7 = E. A. }}
* {{cite journal | vauthors = Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, Fan Y, Kikuchi A, Skoultchi AI, Nakayama KI | title = CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis | journal = Nature Cell Biology | volume = 11 | issue = 2 | pages = 172–82 | date = Feb 2009 | pmid = 19151705 | pmc = 3132516 | doi = 10.1038/ncb1831 | first3 = Shun-Ichiro }}
* {{cite journal | vauthors = Rodríguez-Paredes M, Ceballos-Chávez M, Esteller M, García-Domínguez M, Reyes JC | title = The chromatin remodeling factor CHD8 interacts with elongating RNA polymerase II and controls expression of the cyclin E2 gene | journal = Nucleic Acids Research | volume = 37 | issue = 8 | pages = 2449–60 | date = May 2009 | pmid = 19255092 | pmc = 2677868 | doi = 10.1093/nar/gkp101 | first3 = J. C. }}
* {{cite journal | vauthors = Yates JA, Menon T, Thompson BA, Bochar DA | title = Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8 | journal = FEBS Letters | volume = 584 | issue = 4 | pages = 689–93 | date = Feb 2010 | pmid = 20085832 | doi = 10.1016/j.febslet.2010.01.022 }}
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CHD8