The ATP-dependent chromatin-remodeling complex, Rsc, was originally identified in yeast. It has a subunit composition similar to the well-characterized SWI/SNF: 2 subunits are shared between the two complexes and at least 4 others are homologous. However, the function of Rsc is distinct from SWI/SNF. Rsc is essential for the mitotic growth of yeast, whereas SWI/SNF is not. Rsc mutants are arrested at the G2/M transition during the cell cycle, and the arrest is dependent on spindle-checkpoint genes. The mutants are also more sensitive to microtubule- destabilizing drugs. These data suggest that Rsc may play a role in mitosis, perhaps by stabilizing mitotic spindle formation or have a function at kinetochores. We have previously purified several ATP-dependent chromatin remodeling complexes from human that are closely related to either yeast SWI/SNF or Rsc. By microsequencing and cloning, we now identified the BAF180 subunit of human SWI/SNF-B complex as a human homologue of yeast Rsc subunits, Rsc1, Rsc2 and Rsc4. It has the same set of biochemical motifs as the three Rsc subunits: 6 bromodomains, 2 BAH regions, and a minor-groove binding domain. Database search of the completed genome database of human, Drosophila and C.elegans showed that BAF180 is the closest homolog of the three Rsc subunits, suggesting human SWI/SNF-B as a human version of Rsc. We renamed this complex as PBAF (for Polybromo-associated BAF complex). We subsequently identified many other subunits of human PBAF complex and found a number of them to be identical to those in human SWI/SNF. We also demonstrated that BAF180 localizes at kinetochores of mitotic chromosomes, consistent with a function for PBAF during mitosis. Part of this work has been published in Proc. Natl. Acad. Sci. USA. As a continuation of this project, we have identified three possible new components of this complex. We have obtained antibody against one of them, BAF200. With this antibody, we have been able to show that BAF200 is indeed an intrinsic component of this complex. BAF200 contains a domain found in a component of yeast RSC complex, implying that BAF200 may be a conserved functional subunit within RSC family of complexes. We are currently performing siRNA knockdown experiments to identify genes regulated by BAF200 and its associated complex; using both microarray profiling and candidate gene approach, some genes have been identified, and we are now doing chromatin-IP analysis to determine if these genes are directly regulated by PBAF complex.
| Yan, Zhijiang; Cui, Kairong; Murray, Darryl M et al. (2005) PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes. Genes Dev 19:1662-7 |
| Wang, W (2003) The SWI/SNF family of ATP-dependent chromatin remodelers: similar mechanisms for diverse functions. Curr Top Microbiol Immunol 274:143-69 |
| Xue, Y; Canman, J C; Lee, C S 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 97:13015-20 |
