The DNA-binding properties of the ARID-containing subunits of yeast and mammalian SWI/SNF complexes

Abstract

SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that are highly conserved from yeast to human. From yeast to human the complexes contain a subunit with an ARID (A-T-rich interaction domain) DNA-binding domain. In yeast this subunit is SWI1 and in human there are two closely related alternative subunits, p270 and ARID1B. We describe here a comparison of the DNA-binding properties of the yeast and human SWI/SNF ARID-containing subunits. We have determined that SWI1 is an unusual member of the ARID family in both its ARID sequence and in the fact that its DNA-binding affinity is weaker than that of other ARID family members, including its human counterparts, p270 and ARID1B. Sequence analysis and substitution mutagenesis reveals that the weak DNA-binding affinity of the SWI1 ARID is an intrinsic feature of its sequence, arising from specific variations in the major groove interaction site. In addition, this work confirms the finding that p270 binds DNA without regard to sequence specificity, excluding the possibility that the intrinsic role of the ARID is to recruit SWI/SNF complexes to specific promoter sequences. These results emphasize that care must be taken when comparing yeast and higher eukaryotic SWI/SNF complexes in terms of DNA-binding mechanisms.

<i>ARID1B</i>-mediated disorders: Mutations and possible mechanisms

“…ARID1B was found to bind to DNA without sequence specificity and is a component of BAF complexes containing either BRM or BRG1 (22,23). However, ARID1B and ARID1A are coincides with the results of previous studies.…”

“…ARID consists of approximately 100 amino acid residues and has been found to bind to DNA without sequence specificity (22,23). Missense mutations in this domain are likely to disrupt the DNA-binding ability of ARID1B and compromise the function of the BAF complex.…”

Mechanisms of ATP dependent chromatin remodeling

“…The ARID domain in the Dead ringer protein has been shown to have DNAsequence specific binding; whereas ARID from OSA binds DNA with no sequence specificity [51,[55][56][57]. The ARID domain from yeast Swi1 is not a typical member of the ARID family, because it likely has weaker DNA binding affinity due to changes in key residues that normally interact with the major groove of DNA [58]. Swi3 has two known domains that have affinity for nucleosomes and DNA that are called SWIRM and SANT.…”

An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer

“…Here we report the discovery of ARID1A as a candidate TSG in the T47D breast cancer cell line by using this approach. ARID1A encodes a human homolog of yeast SWI1, which contains a DNA-binding motif (AT-rich interactive domain, ARID) and is an integral member of the hSWI/SNF complex, an ATPdependent, chromatin-remodeling, multiple-subunit enzyme (Takeuchi et al, 1997(Takeuchi et al, , 1998Dallas et al, 1998Dallas et al, , 2000Wang et al, 2004;Wilsker et al, 2004;Patsialou et al, 2005). An increasing body of evidence has demonstrated that SWI/SNF complexes have important roles in gene regulation (Winston and Carlson, 1992;Carlson and Laurent, 1994;Hirschhorn et al, 1995;Kennison, 1995;Sudarsanam et al, 1999Sudarsanam et al, , 2000, cell proliferation (Nagl et al, 2005(Nagl et al, , 2006(Nagl et al, , 2007 and development (Carlson and Laurent, 1994;Kennison, 1995).…”