CHD8
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| Location (UCSC) | Chr 14: 21.39 – 21.46 Mb | Chr 14: 52.44 – 52.5 Mb | |||||||
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Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.[5][6]
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
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]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000100888 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000053754 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 10997877.
- ^ "Entrez Gene: CHD8 chromodomain helicase DNA binding protein 8".
- ^ PMID 19151705.
- ^ PMID 23568486.
- ^ PMID 18378692.
- PMID 22083958.
- PMID 25989142.
- PMID 33859315.
- PMID 24998929.
- PMID 28671691.
- PMID 25294932.
- PMID 25752243.
External links
- Human CHD8 genome location and CHD8 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q9HCK8 (Chromodomain-helicase-DNA-binding protein 8) at the PDBe-KB.
Further reading
- Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. PMID 12168954.
- Epplen C, Epplen JT (January 1994). "Expression of (cac)n/(gtg)n simple repetitive sequences in mRNA of human lymphocytes". Human Genetics. 93 (1): 35–41. S2CID 22998633.
- Sakamoto I, Kishida S, Fukui A, Kishida M, Yamamoto H, Hino S, et al. (October 2000). "A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation". The Journal of Biological Chemistry. 275 (42): 32871–8. PMID 10921920.
- Kobayashi M, Hanai R (September 2001). "M phase-specific association of human topoisomerase IIIbeta with chromosomes". Biochemical and Biophysical Research Communications. 287 (1): 282–7. PMID 11549288.
- Kobayashi M, Kishida S, Fukui A, Michiue T, Miyamoto Y, Okamoto T, et al. (February 2002). "Nuclear localization of Duplin, a beta-catenin-binding protein, is essential for its inhibitory activity on the Wnt signaling pathway". The Journal of Biological Chemistry. 277 (8): 5816–22. PMID 11744694.
- Nishiyama M, Nakayama K, Tsunematsu R, Tsukiyama T, Kikuchi A, Nakayama KI (October 2004). "Early embryonic death in mice lacking the beta-catenin-binding protein Duplin". Molecular and Cellular Biology. 24 (19): 8386–94. PMID 15367660.
- Lin KT, Lu RM, Tarn WY (October 2004). "The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo". Molecular and Cellular Biology. 24 (20): 9176–85. PMID 15456888.
- Ishihara K, Oshimura M, Nakao M (September 2006). "CTCF-dependent chromatin insulator is linked to epigenetic remodeling". Molecular Cell. 23 (5): 733–42. PMID 16949368.
- Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. S2CID 14294292.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. PMID 17081983.
- Yuan CC, Zhao X, Florens L, Swanson SK, Washburn MP, Hernandez N (December 2007). "CHD8 associates with human Staf and contributes to efficient U6 RNA polymerase III transcription". Molecular and Cellular Biology. 27 (24): 8729–38. PMID 17938208.
- Thompson BA, Tremblay V, Lin G, Bochar DA (June 2008). "CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes". Molecular and Cellular Biology. 28 (12): 3894–904. PMID 18378692.
- Caldon CE, Sergio CM, Schütte J, Boersma MN, Sutherland RL, Carroll JS, et al. (September 2009). "Estrogen regulation of cyclin E2 requires cyclin D1 but not c-Myc". Molecular and Cellular Biology. 29 (17): 4623–39. PMID 19564413.
- Nishiyama M, Oshikawa K, Tsukada Y, Nakagawa T, Iemura S, Natsume T, et al. (February 2009). "CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis". Nature Cell Biology. 11 (2): 172–82. PMID 19151705.
- Rodríguez-Paredes M, Ceballos-Chávez M, Esteller M, García-Domínguez M, Reyes JC (May 2009). "The chromatin remodeling factor CHD8 interacts with elongating RNA polymerase II and controls expression of the cyclin E2 gene". Nucleic Acids Research. 37 (8): 2449–60. PMID 19255092.
- Yates JA, Menon T, Thompson BA, Bochar DA (February 2010). "Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8" (PDF). FEBS Letters. 584 (4): 689–93. S2CID 9956275.
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