Purification and biochemical heterogeneity of the mammalian SWI-SNF complex.

Abstract

We have purified distinct complexes of nine to 12 proteins [referred to as BRG1‐associated factors (BAFs)] from several mammalian cell lines using an antibody to the SWI2‐SNF2 homolog BRG1. Microsequencing revealed that the 47 kDa BAF is identical to INI1. Previously INI1 has been shown to interact with and activate human immunodeficiency virus integrase and to be homologous to the yeast SNF5 gene. A group of BAF47‐associated proteins were affinity purified with antibodies against INI1/BAF47 and were found to be identical to those co‐purified with BRG1, strongly indicating that this group of proteins associates tightly and is likely to be the mammalian equivalent of the yeast SWI‐SNF complex. Complexes containing BRG1 can disrupt nucleosomes and facilitate the binding of GAL4‐VP16 to a nucleosomal template similar to the yeast SWI‐SNF complex. Purification of the complex from several cell lines demonstrates that it is heterogeneous with respect to subunit composition. The two SWI‐SNF2 homologs, BRG1 and hbrm, were found in separate complexes. Certain cell lines completely lack BRG1 and hbrm, indicating that they are not essential for cell viability and that the mammalian SWI‐SNF complex may be tailored to the needs of a differentiated cell type.

The SWI/SNF complex and cancer

“…The BAF47 subunit of the SWI/SNF complex is a bona fide tumor suppressor INI1 was initially discovered as a protein that binds HIV integrase (Kalpana et al, 1994) and was later shown to be identical to the BAF47 component of the SWI/SNF chromatin-remodeling complex (Wang et al, 1996a). The gene that encodes BAF47 is located on chromosome 22q11, a region that is frequently rearranged in pediatric rhabdoid tumors (Versteege et al, 1998).…”

MLL: How complex does it get?

“…Other proteins found in the MLL complex also have this chromatin remodeling potential. BRM, BAF170, BAF155, and INI1 associate with MLL and are all components of the SWI/SNF ATP-dependent nucleosome remodeling complex [Wang et al, 1996]. A number of proteins found in this MLL complex are members of the TFIID complex.…”

The requirement for SNF5/INI1 in adipocyte differentiation highlights new features of malignant rhabdoid tumors

“…Different SWI/SNF complexes with variable subunit compositions have been described in mammals (Wang et al, 1996). They play a major role in transcription regulation through physical and functional interactions with transcriptional activators or repressors (Sif et al, 2001) and are involved in a variety of cellular processes, including the regulation of cell growth and differentiation (Roberts and Orkin, 2004).…”