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Gene Review

CHD4  -  chromodomain helicase DNA binding protein 4

Homo sapiens

Synonyms: ATP-dependent helicase CHD4, CHD-4, Chromodomain-helicase-DNA-binding protein 4, Mi-2 autoantigen 218 kDa protein, Mi-2b, ...
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Disease relevance of CHD4


High impact information on CHD4

  • NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex [4].
  • Furthermore, the functional importance of the association of Mi-2 beta and RFP was confirmed by using Rfp-/- fibroblasts [5].
  • On the other hand, we demonstrated that Mi-2 and BRG1 were associated with each other and that the bromodomain region of BRG1 strongly suppressed transactivation by the amino-terminal region of Mi-2 beta [5].
  • CHD4 (also called Mi-2beta) is a component of a histone-deacetylase-2 (HDAC2)-containing complex, the nucleosome remodeling and deacetylating (NRD) complex [6].
  • No differences were found between patients with autoantibodies to different fragments of the Mi-2 beta antigen, except for a potentially increased risk of cancer in patients with antibodies directed to the N-terminal fragment of the autoantigen [3].

Biological context of CHD4

  • ATR's association with CHD4 and HDAC2 suggests that there may be a linkage between ATR's role in mediating checkpoints induced by DNA damage and chromatin modulation via remodeling and deacetylation [6].
  • Finally, we show that interaction with CHD4 is regulated by alternative splicing of the NAB2 mRNA [4].
  • Using a genetic screen, we identify Mi2beta, a component of the recently identified NURD histone deacetylase complex, as a protein that binds directly to the E7 zinc finger [2].
  • The findings that Mi-2 beta interacts with both transactivating and repressing proteins and directly associates with another chromatin remodeling protein, BRG1, provide new insight into the formation of multiprotein supercomplex involved in transcriptional regulation [5].

Associations of CHD4 with chemical compounds


Other interactions of CHD4

  • To understand the molecular mechanisms underlying NAB repression, we found that EGR activity is modulated by at least two repression domains within NAB2, one of which uniquely requires interaction with the CHD4 (chromodomain helicase DNA-binding protein 4) subunit of the NuRD (nucleosome remodeling and deacetylase) chromatin remodeling complex [4].
  • We determined the structure of a PHD finger from the transcriptional cofactor Mi2beta and investigated the suitability of this domain as a scaffold for presenting selected binding functions [8].


  1. The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Zhang, Y., LeRoy, G., Seelig, H.P., Lane, W.S., Reinberg, D. Cell (1998) [Pubmed]
  2. The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. Brehm, A., Nielsen, S.J., Miska, E.A., McCance, D.J., Reid, J.L., Bannister, A.J., Kouzarides, T. EMBO J. (1999) [Pubmed]
  3. Clinical characteristics of patients with myositis and autoantibodies to different fragments of the Mi-2 beta antigen. Hengstman, G.J., Vree Egberts, W.T., Seelig, H.P., Lundberg, I.E., Moutsopoulos, H.M., Doria, A., Mosca, M., Vencovsky, J., van Venrooij, W.J., van Engelen, B.G. Ann. Rheum. Dis. (2006) [Pubmed]
  4. NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex. Srinivasan, R., Mager, G.M., Ward, R.M., Mayer, J., Svaren, J. J. Biol. Chem. (2006) [Pubmed]
  5. Mi-2 beta associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities. Shimono, Y., Murakami, H., Kawai, K., Wade, P.A., Shimokata, K., Takahashi, M. J. Biol. Chem. (2003) [Pubmed]
  6. Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4. Schmidt, D.R., Schreiber, S.L. Biochemistry (1999) [Pubmed]
  7. The gene expression profile of human umbilical vein endothelial cells stimulated by tumor necrosis factor alpha using DNA microarray analysis. Murakami, T., Mataki, C., Nagao, C., Umetani, M., Wada, Y., Ishii, M., Tsutsumi, S., Kohro, T., Saiura, A., Aburatani, H., Hamakubo, T., Kodama, T. J. Atheroscler. Thromb. (2000) [Pubmed]
  8. Engineering a protein scaffold from a PHD finger. Kwan, A.H., Gell, D.A., Verger, A., Crossley, M., Matthews, J.M., Mackay, J.P. Structure (Camb.) (2003) [Pubmed]
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