SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions?

For further thought, we have included some additional questions. There has been a significant body of new data on SWI/SNF and related complexes, and there are many interesting and important issues that will likely be clarified in the near future.Is the specificity in the function of the SWI/SNF complex due to targeting of the complex to the appropriate genes (such as through interactions with DNA-bound transcription factors [direct mechanism]), or does the SWI/SNF complex globally facilitate nucleosome mobility in a manner that affects the transcriptional state of only a subset of genes that are sensitive to such changes in chromatin structure (indirect mechanism)?SWI/SNF complex, RSC, and NURF appear to comprise about 4 to 15 polypeptides. What is the function of the polypeptides in SWI/SNF and related complexes that do not possess the conserved NTP-binding motif? For example, are some of the other subunits involved in regulation of the activity of the complex, interactions with other transcription factors, or subcellular localization?Is the SWI/SNF complex an integral component of the RNA polymerase II holoenzyme? There are conflicting data regarding this point (3xCairns, B.R, Lorch, Y, Li, Y, Lacomis, L, Erjument-Bromage, H, Tempst, P, Du, J, Laurent, B, and Kornberg, R.D. Cell. 1996; 87: 1249–1260Abstract | Full Text | Full Text PDF | PubMed | Scopus (479)See all References, 19xWilson, C.J, Chao, D.M, Imbalzano, A.N, Schnitzler, G.R, Kingston, R.E, and Young, R.A. Cell. 1996; 84: 235–244Abstract | Full Text | Full Text PDF | PubMed | Scopus (303)See all References).It has been shown that SWI/SNF complex can facilitate the nucleosome-inhibited binding of GAL4 derivatives to DNA in a mononucleosome. Analogously, NURF can facilitate the nucleosome-inhibited binding of the GAGA factor to DNA in a mononucleosome. In contrast, however, the binding of GAL4 derivatives, GAGA factor, and NF-E2 do not appear to be inhibited by packaging of DNA into extended nucleosome arrays (as opposed to mononucleosomes), even in the absence of ATP-dependent SWI/SNF-like activities (11xPazin, M.J, Kamakaka, R.T, and Kadonaga, J.T. Science. 1994; 266: 2007–2011Crossref | PubMedSee all References, 16xTsukiyama, T and Wu, C. Cell. 1995; 83: 1011–1020Abstract | Full Text PDF | PubMed | Scopus (443)See all References, 1xArmstrong, J.A and Emerson, B.M. Mol. Cell. Biol. 1996; 16: 5634–5644PubMedSee all References). What is the basis for this apparent difference? Are internucleosomal interactions important for the proper functioning of transcription factors?Do transcriptional activation domains participate in the SWI/SNF complex-facilitated binding of factors to chromatin? Studies from different laboratories have led to different conclusions regarding this point. It appears, however, that activation domains can increase the binding of factors to chromatin in vivo. In those instances, is the activation domain directly involved in the binding of the factor to the nucleosome (i.e., does it interact directly with the core histones and/or the DNA), or is it required for cooperative binding with another transcription factor?Lastly, what happens to the nucleosomes upon addition of SWI/SNF complex (or RSC or NURF) and ATP? This process is often referred to as “remodeling.” Is remodeling the dissociation of some or all of the core histones from DNA, is it a conformational change, or is it some other alteration/modification of the nucleosome?*To whom correspondence should be addressed.