ABSTRACT
PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity in mediating transcription of different interferon-responsive genes. The selectivity by PBAF requires a novel subunit, BAF200, but not the previously described PBAF-specificity subunit, BAF180 (Polybromo). Our study provides in vivo evidence that PBAF and BAF regulate expression of distinct genes, and suggests that BAF200 plays a key role in PBAF function.
Subject(s)
Chromatin Assembly and Disassembly , Chromosomal Proteins, Non-Histone/metabolism , Transcription Factors/metabolism , Chromosomal Proteins, Non-Histone/chemistry , Chromosomal Proteins, Non-Histone/genetics , Gene Expression Regulation/drug effects , HeLa Cells , Humans , In Vitro Techniques , Interferon Type I/pharmacology , Multiprotein Complexes/chemistry , Multiprotein Complexes/metabolism , Protein Subunits , RNA, Small Interfering/genetics , Recombinant Proteins , Transcription Factors/chemistry , Transcription Factors/geneticsABSTRACT
The SWI/SNF family of chromatin-remodeling complexes has been discovered in many species and has been shown to regulate gene expression by assisting transcriptional machinery to gain access to their sites in chromatin. Several complexes of this family have been reported for humans. In this study, two additional complexes are described that belong to the same SWI/SNF family. These new complexes contain as many as eight subunits identical to those found in other SWI/SNF complexes, and they possess a similar ATP-dependent nucleosome disruption activity. But unlike known SWI/SNFs, the new complexes are low in abundance and contain an extra subunit conserved between human and yeast SWI/SNF complexes. This subunit, ENL, is a homolog of the yeast SWI/SNF subunit, ANC1/TFG3. Moreover, ENL is a fusion partner for the gene product of MLL that is a common target for chromosomal translocations in human acute leukemia. The resultant MLL-ENL fusion protein associates and cooperates with SWI/SNF complexes to activate transcription of the promoter of HoxA7, a downstream target essential for oncogenic activity of MLL-ENL. Our data suggest that human SWI/SNF complexes show considerable heterogeneity, and one or more may be involved in the etiology of leukemia by cooperating with MLL fusion proteins.