CHD4

{{Short description|Protein-coding gene in the species Homo sapiens}}

Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the CHD4 gene.{{cite journal | vauthors = Seelig HP, Moosbrugger I, Ehrfeld H, Fink T, Renz M, Genth E | title = The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation | journal = Arthritis and Rheumatism | volume = 38 | issue = 10 | pages = 1389–1399 | date = October 1995 | pmid = 7575689 | doi = 10.1002/art.1780381006 }}{{cite journal | vauthors = Seelig HP, Renz M, Targoff IN, Ge Q, Frank MB | title = Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen | journal = Arthritis and Rheumatism | volume = 39 | issue = 10 | pages = 1769–1771 | date = October 1996 | pmid = 8843877 | doi = 10.1002/art.1780391029 | doi-access = }}{{cite web | title = Entrez Gene: CHD4 chromodomain helicase DNA binding protein 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1108}} CHD4 is the core nucleosome-remodelling component of the Nucleosome Remodelling and Deacetylase (NuRD) complex.{{cite journal | vauthors = Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL | title = Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex | journal = Nature | volume = 395 | issue = 6705 | pages = 917–921 | date = October 1998 | pmid = 9804427 | doi = 10.1038/27699 | bibcode = 1998Natur.395..917T | s2cid = 4355885 }}{{cite journal | vauthors = Xue Y, Wong J, Moreno GT, Young MK, Côté J, Wang W | title = NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities | journal = Molecular Cell | volume = 2 | issue = 6 | pages = 851–861 | date = December 1998 | pmid = 9885572 | doi = 10.1016/S1097-2765(00)80299-3 | doi-access = free }}{{cite journal | vauthors = Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D | title = The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities | journal = Cell | volume = 95 | issue = 2 | pages = 279–289 | date = October 1998 | pmid = 9790534 | doi = 10.1016/S0092-8674(00)81758-4 | doi-access = free }}

Function

The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein.

Interactions

CHD4 has been shown to interact with HDAC1,{{cite journal | vauthors = Yao YL, Yang WM | title = The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 43 | pages = 42560–42568 | date = October 2003 | pmid = 12920132 | doi = 10.1074/jbc.M302955200 | doi-access = free }}{{cite journal | vauthors = Grozinger CM, Hassig CA, Schreiber SL | title = Three proteins define a class of human histone deacetylases related to yeast Hda1p | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 9 | pages = 4868–4873 | date = April 1999 | pmid = 10220385 | pmc = 21783 | doi = 10.1073/pnas.96.9.4868 | doi-access = free | bibcode = 1999PNAS...96.4868G }}{{cite journal | vauthors = Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL | title = Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex | journal = Nature | volume = 395 | issue = 6705 | pages = 917–921 | date = October 1998 | pmid = 9804427 | doi = 10.1038/27699 | s2cid = 4355885 | bibcode = 1998Natur.395..917T }} Histone deacetylase 2,{{cite journal | vauthors = Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R | title = A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 9 | pages = 7234–7239 | date = February 2003 | pmid = 12493763 | doi = 10.1074/jbc.M208992200 | doi-access = free}}{{cite journal | vauthors = Schmidt DR, Schreiber SL | title = Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4 | journal = Biochemistry | volume = 38 | issue = 44 | pages = 14711–14717 | date = November 1999 | pmid = 10545197 | doi = 10.1021/bi991614n | citeseerx = 10.1.1.559.7745 }} MTA2, SATB1{{cite journal | vauthors = Yasui D, Miyano M, Cai S, Varga-Weisz P, Kohwi-Shigematsu T | title = SATB1 targets chromatin remodelling to regulate genes over long distances | journal = Nature | volume = 419 | issue = 6907 | pages = 641–645 | date = October 2002 | pmid = 12374985 | doi = 10.1038/nature01084 | s2cid = 25822700 | bibcode = 2002Natur.419..641Y | url = https://digital.library.unt.edu/ark:/67531/metadc733622/ }} and Ataxia telangiectasia and Rad3 related.

Clinical

Mutations in this gene have been associated with a condition known as Sifrim-Hitz-Weiss syndrome.Weiss K, Lazar HP, Kurolap A, Martinez AF, Paperna T, Cohen L, Smeland MF, Wallen S, Solveig H, Keren B, Terhal P, Irving M, Takaku M, Roberts JD, Petrovich RM, Schrier Vergano SA11,12, Kenney A11, Hove H13, DeChene E, Quinonez SC, Colin E, Ziegler A, Rumple M, Jain M, Monteil D, Roeder ER, Nugent K, van Haeringen A, Gambello M, Santani A, Medne L, Krock B, Skraban CM, Zackai EH, Dubbs HA, Smol T, Ghoumid J, Parker M, Wright M, Turnpenny P, Clayton-Smith J, Metcalfe K, Kurumizaka H, Gelb BD, Baris Feldman H, Campeau PM34, Muenke M5, Wade PA, Lachlan K (2019) The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis. Genet Med This condition is characterized by

Brain anomalies
Macrocephaly
Deafness
Ophthalmic abnormalities
Dysmorphic features
Congenital heart defects
Hypogonadism in males
Skeletal and limb anomalies
Global developmental delay
Mild to moderate intellectual disability

References

External links

{{UCSC gene info|CHD4}}