DEVELOPMENTAL REGULATION OF ZBU1, A DNA-BINDING MEMBER OF THE SWI2 SNF2 FAMILY/

The SWI2/SNF2 gene family has been implicated in a wide variety of pro cesses, involving regulation of DNA structure and chromatin configurat ion, mitotic chromosome segregation, and DNA repair. Here we report th e characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily. Zbu1 was isolated in this study by its affinity for a si te in the myosin light chain 1/3 enhancer. The protein has single-stra nded DNA-dependent ATPase activity, includes seven helicase motifs, an d a RING finger motif that is shared exclusively by the RAD5, spRAD8, and RAD16 family members. During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neo natal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain. In adult human tissues, alternatively spl iced Zbu1 transcripts are ubiquitous with highest expression in these tissues. Gene expression is also dramatically induced in human tumor l ines and in Li-Fraumeni fibroblast cultures, suggesting that it is abe rrantly regulated in malignant cells. The developmental profile of Zbu 1 gene expression and the association of the protein with a tissue-spe cific transcriptional regulatory element distinguish it from other mem bers of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product. (C) 1997 Academic Press.