Citation/Abstract

The SWIRM domain is a novel module found in a variety of chromatin regulatory proteins including the Swi3 and Rsc8 subunits of the SWI/SNF-family of chromatin remodeling complexes and the Ada2 and BHC110/LSD1 subunits of chromatin modification complexes. Here I present the high-resolution crystal structure of the SWIRM domain from Swi3 and characterize the in vitro and in vivo function of the SWIRM domains from Swi3 and Rsc8. The structure of the SWIRM domain from Swi3 reveals a novel 4-helix bundle containing a psuedo 2-fold axis and a helix-turn-helix motif that is commonly found in DNA binding proteins. Consistent with these structural findings, I demonstrate that the Swi3 SWIRM domain binds free DNA and mononucleosomes with high and comparable affinity, suggesting that the SWIRM domain of Swi3 may play a role in nucleosomal targeting of the SWI/SNF complex. Solution studies also reveal that the SWIRM domains from both Rsc8 and Swi3 play essential roles in the proper assembly and in vivo functions of the RSC and SWI/SNF complexes, respectively. Mutagenesis studies reveal that a subset of Swi3 SWIRM substitution mutants display growth defects in vivo and also show impaired DNA binding activity in vitro . Together, these data suggest that the SWIRM domain is a nucleosome targeting module that functions through DNA recognition.