SWI/SNF protein

In addition to a potential role of HMGB proteins in nucleosome assembly, it has recently become apparent that many chromatin remodeling complexes either contain, or can associate with, a polypeptide containing an HMG-box homologous to the HMGBl B domain (Table 2). Examples of such complexes include the BAF (a mammalian SWI/SNF related complex [106]) and the Drosophila BRM (brahma)... 

Studies with native and reconstituted chromatin show that phosphorylated HI destabilize chromatin structure [62,63]. Phosphorylation of HI increases the protein s mobility in the nucleus and weakens its interaction with chromatin [64,65]. In studies with avian fibroblasts transfected with H5 (an HI variant), H5 was shown to inhibit proliferation in normal fibroblasts but not in transformed cells, in which H5 was phosphorylated. Aubert et al. proposed that phosphorylated H5 lacked the ability to condense chromatin [66]. The greater affinity of the dephosphorylated relative to phosphorylated HI for chromatin may interfere with the performance of chromatin remodeling agents. For example, dephosphorylated, but not phosphorylated, HI inhibited chromatin remodeling by SWI/SNF [67]. Thus, these and other studies provide support for the idea that an increase in the phosphorylation of HI leads to destabilization of the chromatin [24]. 

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]. 

Travers, A.A. (2003) Priming the nucleosome a role for HMGB proteins EMBO Rep. 4, 131-136. Katsani, K.R., Mahmoudi, T., and Verrijzer, C.P. (2003) Selective gene regulation by SWI/SNF related chromatin remodeling factors. Curr. Top. Microbiol. Immunol. 274, 113-142. 

Reeves, R. (2001) Molecular biology of HMGA proteins hubs of nuclear function. Gene 277, 63-81. Wang, W., Chi, T., Xue, Y., Zhou, S., Kuo, A., and Crabtree, G.R. (1998) Architectural DNA binding by a high-mobility-group/kinesin-like subunit in mammalian SWI/SNF-related complexes. Proc. Natl. Acad. Sci. USA 95, 492 98. 

Dallas, P.B., Pacchione, S., Wilsker, D., Bowrin, V., Kobayashi, R., and Moran, E. (2000) The human SWI-SNF complex protein p270 is an ARID family member with non-sequence-specific DNA binding activity. Mol. Cell. Biol. 20, 3137-3146. 

Cairns, B.R., Erdjument-Bromage, H., Tempst, P., Winston, F., and Kornberg, R.D. (1998) Two actin-related proteins are shared functional components of the chromatin-remodeling complexes RSC and SWI/SNF. Mol. Cell 2, 639-651. 

Other protein complexes also have a role in activating transcription of the GAL genes. These may include the SAGA complex for histone acetylation, the SWI/SNF complex for nucleosome remodeling, and the mediator complex. Figure 28-29 provides an idea of the complexity of protein interactions in the overall process of transcriptional activation in eukaryotic cells. 

The effects of DNA-binding transactivators on Pol II are mediated by coactivator protein complexes such as TFIID or mediator. The modular structures of the transactivators have distinct activation and DNA-binding domains. Other protein complexes, including histone acetyltransferases such as GCN5-ADA2-ADA3 and ATP-dependent complexes such as SWI/SNF and NURF, reversibly remodel chromatin structure. 

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