NuRD complex

NuRD complex Human MTAl, MTA2, HDACl, HDAC2, MBD2, MBD3 cohesion [299]. 

To date only repressive functions have been ascribed to the NuRD complex. It has been suggested that in Drosophila its interaction with the Hunchback and... 

The co-repressor KAP-1 functionally links the DNA-binding Kruppel-associated box zinc finger proteins to the NURD complex by recruiting the Mi-2a subunit. [251]. This interaction requires a tandem PHD/bromodomain motif in which the individual domains appear to act together as a functional unit. The nature of any possible acetylated lysine targets of the bromodomain remains unclear but it is not excluded that this domain could bind to an acetylated lysine in Mi-2a rather than to an acetylated histone tail. 

Feng, Q. and Zhang, Y. (2003) The NuRD complex linking histone modification to nucleosome remodeling. Curr. Top. Microbiol. Immunol. 274, 269-290. 

Solari, F. and Ahringer, J. (2000) NURD-complex genes antagonise Ras-induced vulval development in Caenorhabditis elegans. Curr. Bio. 10, 223-226. 

Fujita, N., Jaye, D.L., Kajita, M., Geigerman, C., Moreno, C.S., and Wade, P.A. (2003) MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113, 207-219. 

MLL (also named ALL-1, HRX, and HTRX), the human homolog of Drosophila trithorax, is a SET domain protein that methylates H3 at Lys-4. The enzymatic activity was enhanced with H3 acetylated at Lys-9 or Lys-14. MLL is a component of a large multiprotein complex composed of greater than 29 proteins, including TFIID, SWI/SNF remodeling complex and NuRD, a histone deacetylase complex. MLL binds to the promoter of Hox genes and regulates their expression [202,203]. 

The unmodified and Lys-9 methylated FI3 tail binds specifically to the HDAC complex NuRD. Methylation at Lys-4 prevents this interaction. A H3 tail methylated at Lys-9 does not affect activity of mammalian Set9. Methylation at Lys-4 does not alter activity of G9a, but does prevent the tail being a substrate for Suv39hl [198]. 

Zegerman, P., Canas, B., Pappin, D., and Kouzarides, T. (2002) Histone H3 lysine 4 methylation disrupts binding of nucleosome remodelling and deacetylase (NuRD) repressor complex. J. Biol. Chem. 277, 11621-11624. 

MBD2a Contain MBD domain and (glycine-arginine)n domain Transcriptional repressor, a component of the Mi2/NuRD deacetylase complex MBD2b Co-localizes with heavily methylated satellite DNA in mouse cells ... 

MBD3 Contains MBD domain and a C-terminal stretch of 12 glutamic acid residues mammalian protein does not bind methylated DNA in vivo or in vitro A component of the Mi2/NuRD and SMRT/HDAC5-7 deacetylase complexes Expressed in somatic tissues and in ES cells... 

MBD2 together with MBD3 (previously known as MeCPl) are part of the Mi2/NuRD co-repressor complex [76,89]. So far, no molecular partner proteins have been identified for MBDl this protein has multiple splice variants and can repress transcription through HDAC-dependent, as well as HDAC-independent mechanisms [87,88]. 

As mentioned earlier, MeCP2 is not the only protein that associates with HD AC activities. Both MBD2 and MBDl repress transcription in histone deacetylation-dependent manner. Interestingly, MBD2 was found associated not only with class I histone deacetylases (HDACl and 2) from the Mi2/NuRD corepressor complex but also with class II histone deacetylases in the silencing mediator of retinoic and thyroid receptor (SMRT)/HDAC 5,7 complex [137]. 

Xue, Y., Wong, J., Moreno, G.T., Young, M.K., Cote, J., and Wang, W. (1998) NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol. Cell 2, 851-861. 

Zhang, Y., Ng, H.-H., Erdjument-Bromage, H., Tempst, P., Bird, A., and Reinberg, D. (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 13, 1924-1935. 

Murawsky, C.M., Brehm, A., Badenhorst, P., Lowe, N., Becker, P.B., and Travers, A.A. (2001) Tramtrack69 interacts with the dMi-2 subunit of the Drosophila NuRD chromatin remodeling complex. EMBO Rep. 2, 1089-1094. 

Schultz, D.C., Friedman, J.R., and Rauscher, F.J., 3rd. (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-2a subunit of NuRD, Genes Dev. 15, 428-443. 

Le Guezennec, X., Vermeulen, M., Brinkman, A.B., Hoeijmakers, W.A., Cohen, A., Lasonder, E. and Stunnenberg, H.G. (2006) MBD2/NuRD and MBD3/ NuRD, two distinct complexes with different biochemical and functional properties. Molecular and Cellular Biology, 26, 843-851. 

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