Chromatin Regulator | Alias |
| CHD7 | IS3; KAL5; FLJ20357; FLJ20361; KIAA1416 |
External Links: | Wiki GeneCards NCBI UniProt |
Related histone modifications: | NA
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Introduction | |
| Full Name: Chromodomain helicase DNA-binding protein 7
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CHD7 is a chromatin remodeler belonging to subgroup III of the CHD (chromodomain helicase DNA-binding) family. It contains three conserved regions (CR1-CR3), a SANT domain, and two BRK domains. CHD7 is the primary cause of CHARGE syndrome and plays roles in transcriptional regulation, differentiation, and development (1-6).
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Function and Interaction | |
| CHD7 interacts with Sox2, thus regulating some syndrome-related genes such as Jag1, Gli3, and Mycn (7). CHD7 also interacts with CHD8 both directly and indirectly through additional linker proteins (8). CHD7 localizes to both the nucleoplasm and nucleolus, acting as a modulator of ribosomal RNA transcription. Depletion of CHD7 can result in increasing levels of DNA methylation in the rRNA promoter region, thereby reducing the level of rRNA expression (3). CHD7 is capable of interacting with histone H3 when methylated at lysine 4 (H3K4me) through its chromodomains, and CHD7 binding sites vary as the H3K4me pattern changes during mouse ES cell differentiation, indicating that CHD7 modulates the transcription of several target genes through their enhancer regions (4). CHD7 is regarded as an essential factor during the development of inner ear neuroblasts and inner ear morphogenesis, and mutation of CHD7 can lead to disruption of innervation in the adult posterior crista within the ear and decreased numbers of neural stem cells in the olfactory epithelium (9-11).
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Disease Association | |
| Mutations in CHD7 are the major cause of CHARGE syndrome, which is characterized by heart disease, retarded growth and development and/or central nervous system abnormalities, genital abnormalities and/or hypogonadism, and ear abnormalities and/or deafness (5-6). Mutations in CHD7 also occur in Kallmann syndrome (12-13).
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ChIP-Seq data
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References | |
1. Hall, J.A. and Georgel, P.T. (2007) CHD proteins: a diverse family with strong ties. Biochem Cell Biol, 85, 463-476.
2. Marfella, C.G.A. and Imbalzano, A.N. (2007) The Chd family of chromatin remodelers. Mutat Res-Fund Mol M, 618, 30-40.
3. Zentner, G.E., Hurd, E.A., Schnetz, M.P., Handoko, L., Wang, C.P., Wang, Z.H., Wei, C.L., Tesar, P.J., Hatzoglou, M., Martin, D.M. et al. (2010) CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis. Hum Mol Genet, 19, 3491-3501.
4. Schnetz, M.P., Bartels, C.F., Shastri, K., Balasubramanian, D., Zentner, G.E., Balaji, R., Zhang, X.D., Song, L.Y., Wang, Z.H., LaFramboise, T. et al. (2009) Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res, 19, 590-601.
5. Vissers, L.E.L.M., van Ravenswaaij, C.M.A., Admiraal, R., Hurst, J.A., de Vries, B.B.A., Janssen, I.M., van der Vliet, W.A., Huys, E.H.L.P.G., de Jong, P.J., Hamel, B.C.J. et al. (2004) Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet, 36, 955-957.
6. Zentner, G.E., Layman, W.S., Martin, D.M. and Scacheri, P.C. (2010) Molecular and Phenotypic Aspects of CHD7 Mutation in CHARGE Syndrome. Am J Med Genet A, 152A, 674-686.
7. Engelen, E., Akinci, U., Bryne, J.C., Hou, J., Gontan, C., Moen, M., Szumska, D., Kockx, C., van IJcken, W., Dekkers, D.H.W. et al. (2011) Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes. Nat Genet, 43, 607-U153.
8. Batsukh, T., Pieper, L., Koszucka, A.M., von Velsen, N., Hoyer-Fender, S., Elbracht, M., Bergman, J.E.H., Hoefsloot, L.H. and Pauli, S. (2010) CHD8 interacts with CHD7, a protein which is mutated in CHARGE syndrome. Hum Mol Genet, 19, 2858-2866.
9. Hurd, E.A., Poucher, H.K., Cheng, K., Raphael, Y. and Martin, D.M. (2010) The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear. Development, 137, 3139-3150.
10. Adams, M.E., Hurd, E.A., Beyer, L.A., Swiderski, D.L., Raphael, Y. and Martin, D.M. (2007) Defects in vestibular sensory epithelia and innervation in mice with loss of chd7 function: Implications for human CHARGE syndrome. J Comp Neurol, 504, 519-532.
11. Layman, W.S., McEwen, D.P., Beyer, L.A., Lalani, S.R., Fernbach, S.D., Oh, E., Swaroop, A., Hegg, C.C., Raphael, Y., Martens, J.R. et al. (2009) Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum Mol Genet, 18, 1909-1923.
12. Jongmans, M.C.J., van Ravenswaaij-Arts, C.M.A., Pitteloud, N., Ogata, T., Sato, N., Claahsen-van der Grinten, H.L., van der Donk, K., Seminara, S., Bergman, J.E.H., Brunner, H.G. et al. (2009) CHD7 mutations in patients initially diagnosed with Kallmann syndrome - the clinical overlap with CHARGE syndrome. Clin Genet, 75, 65-71.
13. Kim, H.G., Kurth, I., Lan, F., Meliciani, I., Wenzel, W., Eom, S.H., Kang, G.B., Rosenberger, G., Tekin, M., Ozata, M. et al. (2008) Mutations in CHD7, Encoding a Chromatin-Remodeling Protein, Cause Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome. Am J Hum Genet, 83, 511-519.
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