Structural and DNA binding properties of ARID domains present in hSWI SNF chromatin remodeling complex subunits

Abstract

The SWI/SNF complexes are multisubunit-containing protein complexes that are involved in chromatin-remodeling processes in the eukaryotic cells. In higher eukaryotes, SWI/SNF complexes contain one or more mutually exclusive AT-rich interaction domain (ARID)-containing proteins as one of the subunit. The SWI/SNF complexes can be further classified into sub complexes. Association of ARID-containing proteins BAF250a (also known as ARID1a) and BAF250b (also known as ARID1b) with the SWI/SNF complex results in BAF-A and BAF-B complexes respectively, whereas the association of ARID-containing BAF200 (also known as ARID2) results in PBAF complex. BAF250a, BAF250b and BAF200 subunits have an AT-rich interaction domain named as ARID. It has been proposed that BAF250a/b and BAF200 subunits likely recruit SWI/SNF complex through ARID domain to heterochromatin that allows transcriptional activation of normally silenced chromatin, thereby regulating the specific gene expression. The ARID is a conserved, all helical DNA binding domain found in several eukaryotic proteins. ARIDs in proteins such as human modulator recognition factor 2 (Mrf2), Drosophila Dead Ringer (Dri), and murine protein Bright were shown to recognize specific AT-rich DNA sequences. The evidences so far suggest that ARIDs of human SWI/SNF complexes interact with DNA without any sequence preference, therefore questioning the recruitment of SWI/SNF complexes by BAF250a to the target genes via its interaction with specific DNA sequences. The structure and functional annotation of BAF250a/b (gt 2200 residues long proteins) remains poorly understood. The folded regions and domain boundaries of these lengthy proteins have not been clearly defined. Likewise, their DNA-binding specificities have not been studied systematically. With this background, we proposed to study the structure and DNA binding specificities of ARID domains in BAF250a, BAF250b, and BAF200 in this thesis...