Chromatin Regulator | Alias |
| CHD4 | Mi-2b; Mi2-BETA; DKFZp686E06161 |
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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CHD4 is a chromatin remodeler belonging to the SNF2 family, a component of the nucleosome remodeling deacetylase (NuRD) complex. It contains a nucleosome-remodeling ATPase domain, two chromodomains, and two plant homeodomain (PHD) fingers and is involved in transcriptional repression, DNA-damage repair, cell-cycle modulation, and cell differentiation (1-6).
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Function and Interaction | |
| CHD4 hydrolyzes ATP, thus allowing histone deacetylases to access chromatin, and it perform its deacetylation function and suppresses transcription using the resulting energy (1). CHD4 is recruited to DNA damage sites and can initiate DNA repair, and it can regulate the deacetylation of p53, thus controlling the G1/S cell-cycle transition (2). CHD4 and CHD3 associate with pericentrin to modulate the integrity and function of the centrosome (7). CHD4 has also been suggested to be associated with transcriptional activation through interacting with methyl transferases and histone acetyltransferases (HATs) (8-10). CHD4 is essential for hematopoietic stem cell differentiation and T cell development (6,10). Furthermore, it is capable of erasing a DNase I-hypersensitive site (11). CHD4 interacts with BRG1, which then regulate vascular Wnt signaling together (9,12).
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Disease Association | |
| NA
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ChIP-Seq data
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References | |
1. Wang, H.B. and Zhang, Y. (2001) Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor. Nucleic Acids Res, 29, 2517-2521.
2. Polo, S.E., Kaidi, A., Baskcomb, L., Galanty, Y. and Jackson, S.P. (2010) Regulation of DNA-damage responses and cell-cycle progression by the chromatin remodelling factor CHD4. Embo Journal, 29, 3130-3139.
3. Zhang, Y., LeRoy, G., Seelig, H.P., Lane, W.S. and Reinberg, D. (1998) The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell, 95, 279-289.
4. Mansfield, R.E., Musselman, C.A., Kwan, A.H., Oliver, S.S., Garske, A.L., Davrazou, F., Denu, J.M., Kutateladze, T.G. and Mackay, J.P. (2011) Plant Homeodomain (PHD) Fingers of CHD4 Are Histone H3-binding Modules with Preference for Unmodified H3K4 and Methylated H3K9. J Biol Chem, 286, 11779-11791.
5. Woodage, T., Basrai, M.A., Baxevanis, A.D., Hieter, P. and Collins, F.S. (1997) Characterization of the CHD family of proteins. P Natl Acad Sci USA, 94, 11472-11477.
6. Yoshida, T., Hazan, I., Zhang, J., Ng, S.Y., Naito, T., Snippert, H.J., Heller, E.J., Qi, X.Q., Lawton, L.N., Williams, C.J. et al. (2008) The role of the chromatin remodeler Mi-2 beta in hematopoietic stem cell self-renewal and multilineage differentiation. Gene Dev, 22, 1174-1189.
7. Sillibourne, J.E., Delaval, B., Redick, S., Sinha, M. and Doxsey, S.J. (2007) Chromatin remodeling proteins interact with pericentrin to regulate centrosome integrity. Mol Biol Cell, 18, 3667-3680.
8. Nakamura, T., Mori, T., Tada, S., Krajewski, W., Rozovskaia, T., Wassell, R., Dubois, G., Mazo, A., Croce, C.M. and Canaani, E. (2002) ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell, 10, 1119-1128.
9. Shimono, Y., Murakami, H., Kawai, K., Wade, P.A., Shimokata, K. and Takahashi, M. (2003) Mi-2 beta associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities. J Biol Chem, 278, 51638-51645.
10. Williams, C.J., Naito, T., Arco, P.G.D., Seavitt, J.R., Cashman, S.M., De Souza, B., Qi, X.Q., Keables, P., Von Andrian, U.H. and Georgopoulos, K. (2004) The chromatin remodeler Mi-2 beta is required for CD4 expression and T cell development. Immunity, 20, 719-733.
11. Ishii, H., Du, H., Zhang, Z., Henderson, A., Sen, R. and Pazin, M.J. (2009) Mi2 beta Shows Chromatin Enzyme Specificity by Erasing a DNase I-hypersensitive Site Established by ACF. J Biol Chem, 284, 7533-7541.
12. Curtis, C.D. and Griffin, C.T. (2012) The Chromatin-Remodeling Enzymes BRG1 and CHD4 Antagonistically Regulate Vascular Wnt Signaling. Mol Cell Biol, 32, 1312-1320.
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