A highly conserved multisubunit enzymic complex, SWI/SNF, participates in the regulation of eukaryote gene expression through its ability to remodel chromatin. While a single component of SWI/SNF, Swi2 or a related protein, can perform this function in vitro, the other components appear to modulate the activity and specificity of the complex in vivo. Here we describe the cloning of hELD/OSA1, a 189KDa human homologue of Drosophila Eld/Osa protein, a constituent of Drosophila SWI/SNF. By comparing conserved peptide sequences in Eld/Osa homologues we define three domains common to all family members. A putative DNA binding domain, or ARID (AT-rich DNA-interacting domain), may function in targetting SWI/SNF to chromatin. Two other domains unique to Eld/Osa proteins, EHD1 and EHD2, map to the C-teminus. We show that EHD2 mediates binding to Brahma-related gene 1 (BRG1), a human homologue of yeast Swi2. EHD1 and EHD2 also appear capable of interacting with each other. Using an antibody raised against EHD2 of hELD/OSA1, we detected Eld/Osa1 in endogenous SWI/SNF complexes derived from mouse brain.
Abbreviations used: ARID, AT-rich DNA-interacting domain; BRM, BRAHMA; BRG1, Brahma-related gene 1; BAF, BRG1/BRM-associated factor; EHD, Eld/Osa homology domains; EST, expressed sequence tag; HA, haemagglutinin; hELD/OSA1, human homologue of Drosophila Eld/Osa protein; HATs, nuclear histone acetyltransferases; ORF, open reading frame; PQRs, proline and glutamine rich regions; 5′-RACE, 5′-rapid amplification of cDNA ends.
- The Biochemical Society, London ©2002