CHD3 explained

Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the CHD3 gene.^{[1] [2]}

Function

This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription. Autoantibodies against this protein are found in a subset of patients with dermatomyositis. Three alternatively spliced transcripts encoding different isoforms have been described.^[3]

Mutations in CHD3 cause a neurodevelopmental syndrome (Snijders Blok-Campeau syndrome) with macrocephaly and impaired speech and language.^[4]

Interactions

CHD3 has been shown to interact with:

• HDAC1,^{[5] [6]}
• Histone deacetylase 2^{[5] [7] [8]} and
• SERBP1.^{[9] [10]}

Further reading

• Bowen NJ, Fujita N, Kajita M, Wade PA . Mi-2/NuRD: multiple complexes for many purposes . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1677 . 1–3 . 52–7 . Mar 2004 . 15020045 . 10.1016/j.bbaexp.2003.10.010 .
• Gieser L, Swaroop A . Expressed sequence tags and chromosomal localization of cDNA clones from a subtracted retinal pigment epithelium library . Genomics . 13 . 3 . 873–6 . Jul 1992 . 1639417 . 10.1016/0888-7543(92)90173-P . 2027.42/29973 . free .
• Seelig HP, Moosbrugger I, Ehrfeld H, Fink T, Renz M, Genth E . The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation . Arthritis and Rheumatism . 38 . 10 . 1389–99 . Oct 1995 . 7575689 . 10.1002/art.1780381006 .
• Seelig HP, Renz M, Targoff IN, Ge Q, Frank MB . Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen . Arthritis and Rheumatism . 39 . 10 . 1769–71 . Oct 1996 . 8843877 . 10.1002/art.1780391029 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Aubry F, Mattéi MG, Galibert F . Identification of a human 17p-located cDNA encoding a protein of the Snf2-like helicase family . European Journal of Biochemistry . 254 . 3 . 558–64 . Jun 1998 . 9688266 . 10.1046/j.1432-1327.1998.2540558.x . free .
• Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL . Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex . Nature . 395 . 6705 . 917–21 . Oct 1998 . 9804427 . 10.1038/27699 . 1998Natur.395..917T . 4355885 .
• Kleiderlein JJ, Nisson PE, Jessee J, Li WB, Becker KG, Derby ML, Ross CA, Margolis RL . CCG repeats in cDNAs from human brain . Human Genetics . 103 . 6 . 666–73 . Dec 1998 . 9921901 . 10.1007/s004390050889 . 23696667 .
• Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K . Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes . Immunity . 10 . 3 . 345–55 . Mar 1999 . 10204490 . 10.1016/S1074-7613(00)80034-5 . free .
• Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP . Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation . Nature Genetics . 23 . 1 . 62–6 . Sep 1999 . 10471500 . 10.1038/12664 . 52868103 .
• Cousin P, Billotte J, Chaubert P, Shaw P . Physical map of 17p13 and the genes adjacent to p53 . Genomics . 63 . 1 . 60–8 . Jan 2000 . 10662545 . 10.1006/geno.1999.6062 .
• Minty A, Dumont X, Kaghad M, Caput D . Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif . The Journal of Biological Chemistry . 275 . 46 . 36316–23 . Nov 2000 . 10961991 . 10.1074/jbc.M004293200 . free .
• Schultz DC, Friedman JR, Rauscher FJ . Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD . Genes & Development . 15 . 4 . 428–43 . Feb 2001 . 11230151 . 312636 . 10.1101/gad.869501 .
• Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T . SATB1 targets chromatin remodelling to regulate genes over long distances . Nature . 419 . 6907 . 641–5 . Oct 2002 . 12374985 . 10.1038/nature01084 . 2002Natur.419..641Y . 25822700 .
• Lemos TA, Passos DO, Nery FC, Kobarg J . Characterization of a new family of proteins that interact with the C-terminal region of the chromatin-remodeling factor CHD-3 . FEBS Letters . 533 . 1–3 . 14–20 . Jan 2003 . 12505151 . 10.1016/S0014-5793(02)03737-7 . 41197943 .
• Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA . MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer . Cell . 113 . 2 . 207–19 . Apr 2003 . 12705869 . 10.1016/S0092-8674(03)00234-4 . 5773916 . free .
• Lee BH, Yoshimatsu K, Maeda A, Ochiai K, Morimatsu M, Araki K, Ogino M, Morikawa S, Arikawa J . Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules . Virus Research . 98 . 1 . 83–91 . Dec 2003 . 14609633 . 10.1016/j.virusres.2003.09.001 .

Notes and References

1. Woodage T, Basrai MA, Baxevanis AD, Hieter P, Collins FS . Characterization of the CHD family of proteins . Proceedings of the National Academy of Sciences of the United States of America . 94 . 21 . 11472–7 . Oct 1997 . 9326634 . 23509 . 10.1073/pnas.94.21.11472 . 1997PNAS...9411472W . free .
2. Ge Q, Nilasena DS, O'Brien CA, Frank MB, Targoff IN . Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen . The Journal of Clinical Investigation . 96 . 4 . 1730–7 . Oct 1995 . 7560064 . 185809 . 10.1172/JCI118218 .
3. Web site: Entrez Gene: CHD3 chromodomain helicase DNA binding protein 3.
4. Snijders Blok L, Rousseau J, Twist J, Ehresmann S, Takaku M, Venselaar H, Rodan LH, Nowak CB, Douglas J, Swoboda KJ, Steeves MA, Sahai I, Stumpel CT, Stegmann AP, Wheeler P, Willing M, Fiala E, Kochhar A, Gibson WT, Cohen AS, Agbahovbe R, Innes AM, Au PY, Rankin J, Anderson IJ, Skinner SA, Louie RJ, Warren HE, Afenjar A, Keren B, Nava C, Buratti J, Isapof A, Rodriguez D, Lewandowski R, Propst J, van Essen T, Choi M, Lee S, Chae JH, Price S, Schnur RE, Douglas G, Wentzensen IM, Zweier C, Reis A, Bialer MG, Moore C, Koopmans M, Brilstra EH, Monroe GR, van Gassen KL, van Binsbergen E, Newbury-Ecob R, Bownass L, Bader I, Mayr JA, Wortmann SB, Jakielski KJ, Strand EA, Kloth K, Bierhals T, Roberts JD, Petrovich RM, Machida S, Kurumizaka H, Lelieveld S, Pfundt R, Jansen S, Deriziotis P, Faive L, Thevenon J, Assoum M, Shriberg L, Kleefstra T, Brunner HG, Wade PA, Fisher SE, Campeau PM . 6 . CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language . Nature Communications . 9 . 1 . 4619 . November 2018 . 30397230 . 6218476 . 10.1038/s41467-018-06014-6 . 2018NatCo...9.4619S .
5. Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL . Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex . Nature . 395 . 6705 . 917–21 . Oct 1998 . 9804427 . 10.1038/27699 . 1998Natur.395..917T . 4355885 .
6. Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D . Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1) . Molecular and Cellular Biology . 22 . 3 . 835–48 . Feb 2002 . 11784859 . 133546 . 10.1128/mcb.22.3.835-848.2002.
7. Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R . A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes . The Journal of Biological Chemistry . 278 . 9 . 7234–9 . Feb 2003 . 12493763 . 10.1074/jbc.M208992200 . free.
8. Hakimi MA, Bochar DA, Schmiesing JA, Dong Y, Barak OG, Speicher DW, Yokomori K, Shiekhattar R . A chromatin remodelling complex that loads cohesin onto human chromosomes . Nature . 418 . 6901 . 994–8 . Aug 2002 . 12198550 . 10.1038/nature01024 . 2002Natur.418..994H . 4344470 .
9. Lemos TA, Passos DO, Nery FC, Kobarg J . Characterization of a new family of proteins that interact with the C-terminal region of the chromatin-remodeling factor CHD-3 . FEBS Letters . 533 . 1–3 . 14–20 . Jan 2003 . 12505151 . 10.1016/s0014-5793(02)03737-7. 41197943 .
10. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . Sep 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .