Snf2 subfamily

The archetype of the Snf2 subfamily, and the entire Snf2 family, is the S cerevisiae Snf2 protein, originally identified genetically because of its role in sugar metabolism (Sucrose Non Fermentation, SNF2) 1, 2 and mating type SWItching (SWI2) 3.

However, these genes were subsequently found to play roles in the regulation of transcription a broader spectrum of genes 4. The link between the function of this complex and chromatin came when Snf2 suppressor mutations were identified in yeast histone genes 5.

Subsequently the proteins were purified and found to form an 11 subunit multi-protein complex capable of ATP-dependent chromatin disruption and termed the SWI/SNF complex 6, 7, 8.

Although Snf2p deletions are viable under certain conditions and affect transcription of only a fraction of all yeast genes during growth under standard laboratory conditions 9, 10, its close homologue Sth1p which forms the core of the RSC complex is essential 11, 7.

Close sequence homologues in a Snf2 subfamily have also been identified and studied in many model organisms, including the D melanogaster Brahma 12 and human hBRM 13 and BRG1 14 proteins. Many of these have been shown to alter the structure of chromatin at the nucleosomal level and to be involved in transcription regulation, although other nucleosome related roles have also been identified 15.

Recent hypotheses have centred on Snf2 subfamily members performing a generally disruptive function on nucleosomes leading either to sliding of the nucleosome 16, 17 or to partial or complete removal of the histone octamer components 18, 19.

Homologues of Snf2p, such as BRG1 and hBRM have been identified as components of megadalton size complexes containing many proteins that are related to components of the yeast SWI/SNF complex 20. However, Snf2 subfamily members have also been reported to interact with additional proteins.

These include histone deacetylases 21, methyl DNA binding proteins 22, histone methyl transferases 23, the retinoblastoma tumor suppressor protein 24, 25, histone chaperones 26, Pol II 27, 28, cohesin 29. These complexes may be recruited to specific regions of the genome through interactions with sequence specific DNA binding proteins (reviewed by 30) or specific patterns of histone modifications 31, 32.

names associated with subfamily members
Snf2p, Sth1p, snf21, SMARCA4, BRG1, BAF190, hSNF2beta, SNF2L4, SMARCA2, hBRM, hSNF2a, SNF2L2, SNF2LA, SYD, splayed, psa-4, brahma
1: Neigeborn, L. and M. Carlson (1984). Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics 108(4): 845-58. PubMed
2: Abrams, E., L. Neigeborn, et al. (1986). Molecular analysis of SNF2 and SNF5, genes required for expression of glucose-repressible genes in Saccharomyces cerevisiae. Mol Cell Biol 6(11): 3643-51. PubMed
3: Breeden, L. and K. Nasmyth (1987). Cell cycle control of the yeast HO gene: cis- and trans-acting regulators. Cell 48(3): 389-97. PubMed
4: Peterson, C. L. and I. Herskowitz (1992). Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell 68(3): 573-83. PubMed
5: Hirschhorn, J. N., S. A. Brown, et al. (1992). Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev 6(12A): 2288-98. PubMed
6: Cote, J., J. Quinn, et al. (1994). Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science 265(5168): 53-60. PubMed
7: Cairns, B. R., Y. Lorch, et al. (1996). RSC, an essential, abundant chromatin-remodeling complex. Cell 87(7): 1249-60. PubMed
8: Smith, C. L., R. Horowitz-Scherer, et al. (2003). Structural analysis of the yeast SWI/SNF chromatin remodeling complex. Nat Struct Biol 10(2): 141-5. PubMed
9: Holstege, F. C., E. G. Jennings, et al. (1998). Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95(5): 717-28. PubMed
10: Sudarsanam, P., V. R. Iyer, et al. (2000). Whole-genome expression analysis of snf/swi mutants of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 97(7): 3364-9. PubMed
11: Laurent, B. C., X. Yang, et al. (1992). An essential Saccharomyces cerevisiae gene homologous to SNF2 encodes a helicase-related protein in a new family. Mol Cell Biol 12(4): 1893-902. PubMed
12: Tamkun, J. W., R. Deuring, et al. (1992). brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell 68(3): 561-72. PubMed
13: Muchardt, C. and M. Yaniv (1993). A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. Embo J 12(11): 4279-90. PubMed
14: Khavari, P. A., C. L. Peterson, et al. (1993). BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366(6451): 170-4. PubMed
15: Becker, P. B. and W. Horz (2002). ATP-dependent nucleosome remodeling. Annu Rev Biochem 71: 247-73. PubMed
16: Whitehouse, I., A. Flaus, et al. (1999). Nucleosome mobilization catalysed by the yeast SWI/SNF complex. Nature 400(6746): 784-7. PubMed
17: Kassabov, S. R., B. Zhang, et al. (2003). SWI/SNF unwraps, slides, and rewraps the nucleosome. Mol Cell 11(2): 391-403. PubMed
18: Lorch, Y., M. Zhang, et al. (1999). Histone octamer transfer by a chromatin-remodeling complex. Cell 96(3): 389-92. PubMed
19: Bruno, M., A. Flaus, et al. (2003). Histone H2A/H2B dimer exchange by ATP-dependent chromatin remodeling activities. Mol Cell 12(6): 1599-606. PubMed
20: Xue, Y., J. C. Canman, et al. (2000). The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes. Proc Natl Acad Sci U S A 97(24): 13015-20. PubMed
21: Sif, S., A. J. Saurin, et al. (2001). Purification and characterization of mSin3A-containing Brg1 and hBrm chromatin remodeling complexes. Genes Dev 15(5): 603-18. PubMed
22: Harikrishnan, K. N., M. Z. Chow, et al. (2005). Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing. Nat Genet 37(3): 254-64. PubMed
23: Xu, W., H. Cho, et al. (2004). A methylation-mediator complex in hormone signaling. Genes Dev 18(2): 144-56. PubMed
24: Dunaief, J. L., B. E. Strober, et al. (1994). The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79(1): 119-30. PubMed
25: Zhang, H. S., M. Gavin, et al. (2000). Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF. Cell 101(1): 79-89. PubMed
26: Moshkin, Y. M., J. A. Armstrong, et al. (2002). Histone chaperone ASF1 cooperates with the Brahma chromatin-remodelling machinery. Genes Dev 16(20): 2621-6. PubMed
27: Wilson, C. J., D. M. Chao, et al. (1996). RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell 84(2): 235-44. PubMed
28: Metivier, R., G. Penot, et al. (2003). Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115(6): 751-63. PubMed
29: Huang, J., J. M. Hsu, et al. (2004). The RSC nucleosome-remodeling complex is required for Cohesin's association with chromosome arms. Mol Cell 13(5): 739-50. PubMed
30: Peterson, C. L. and J. L. Workman (2000). Promoter targeting and chromatin remodeling by the SWI/SNF complex. Curr Opin Genet Dev 10(2): 187-92. PubMed
31: Hassan, A. H., K. E. Neely, et al. (2001). Histone acetyltransferase complexes stabilize swi/snf binding to promoter nucleosomes. Cell 104(6): 817-27. PubMed
32: Agalioti, T., G. Chen, et al. (2002). Deciphering the transcriptional histone acetylation code for a human gene. Cell 111(3): 381-92. PubMed