Mi-2 subfamily

The Mi-2 subfamily includes the human CHD3 and CHD4 proteins, commonly known as Mi-2α and Mi-2β respectively. Mi-2 was isolated as an autoantigen in the human disease dermatomyositis 1. These two proteins and their homologues in D melanogaster and Xenopus have been recognised as core subunits of NuRD complexes which link DNA methylation to chromatin remodelling and deacetylation 2. Human CHD3 differs from CHD4 in having an additional C-terminal domain which directs Mi-2 complexes containing it for a specific transcriptional repression role 3. Because Mi-2 proteins are widely expressed but have specific roles, it has been suggested that their function may be directed by incorporation of different targeting subunits 2, 4. It has been shown that the chromodomains in D melanogaster Mi-2 are required for activity on nucleosome substrates 5.

An additional human member of the Mi-2 subfamily, CHD5, may have a role in neural development and neuroblastomas 6, 7 although its biochemical associations are unknown. The Arabidopsis subfamily member, PKL (swollen roots of mutants resemble a pickle), has been studied and shown to play a role in repressing embryonic genes during plant development 8.

names associated with subfamily members
CHD3, Mi-2a, Mi2alpha, ZFH, PKL, pickle, CHD4, Mi-2b, Mi2beta, let-418, CHD5
1: Seelig, H. P., I. Moosbrugger, et al. (1995). The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum 38(10): 1389-99. PubMed
2: Bowen, N. J., N. Fujita, et al. (2004). Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677(1-3): 52-7. PubMed
3: Schultz, D. C., J. R. Friedman, et al. (2001). Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev 15(4): 428-43. PubMed
4: Korenjak, M., B. Taylor-Harding, et al. (2004). Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell 119(2): 181-93. PubMed
5: Bouazoune, K., A. Mitterweger, et al. (2002). The dMi-2 chromodomains are DNA binding modules important for ATP-dependent nucleosome mobilization. Embo J 21(10): 2430-40. PubMed
6: Thompson, P. M., T. Gotoh, et al. (2003). CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system. Oncogene 22(7): 1002-11. PubMed
7: White, P. S., P. M. Thompson, et al. (2005). Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene 24(16): 2684-94. PubMed
8: Ogas, J., S. Kaufmann, et al. (1999). PICKLE is a CHD3 chromatin-remodeling factor that regulates the transition from embryonic to vegetative development in Arabidopsis. Proc Natl Acad Sci U S A 96(24): 13839-44. PubMed