Disease relevance of CHD4

• The finding that Mi2beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis [1].
• A zinc finger point mutant which is unable to bind Mi2beta and histone deacetylase but is still able to bind Rb fails to overcome cell cycle arrest in osteosarcoma cells [2].
• OBJECTIVES: To assess the clinical implications of autoantibodies directed against different parts of the Mi-2 beta autoantigen in patients with myositis [3].

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

• Initial sequencing analysis identified three of these the genes for squalene epoxydase, chromodomain helicase DNA binding protein 4, and CLP respectively [7].

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].

References