LDB-1 AND SWI/SNF CHROMATIN REMODELING COMPLEX PARTICIPATE IN THE TRANSCRIPTIONAL ACTIVATION BY C. ELEGANS BLIMP1/PRDM1

Abstract

Caenorhabditis elegans BLMP-1 is the ortholog of the human zinc finger and SET domain-containing transcriptional repressor BLIMP1/PRDM1. BLIMP1/PRDM1 and its orthologs are well studied as transcriptional repressors in many species including humans and mice. Interestingly, we found that in C. elegans, BLMP-1 acts as a direct transcriptional activator of bed-3, a gene required for molting and vulval development, providing the first evidence that BLMP-1 can act as a transcriptional activator in C. elegans. To study the role of BLMP-1 as a transcriptional activator, we performed a RNAi screen and identified three possible interacting partners of BLMP-1. Specifically, we found that F58A3.1/LDB-1, F25H8.2 and ZK1128.5/HAM-3 positively regulate bed-3 in a BLMP-1 dependent manner, and that they do not act upstream of BLMP-1. Moreover, F58A3.1/LDB-1 and ZK1128.5/HAM-3 regulate a bed-3 enhancer fragment containing BLMP-1 binding sites. We confirmed that F58A3.1/LDB-1, ZK1128.5/HAM-3, BLMP-1 proteins, as well as their human orthologs, can physically interact with each other. Finally, we found that F58A3.1/LDB-1 and ZK1128.5/HAM-3 not only participate in the transcriptional activation by BLMP-1, but also in the transcriptional repression by BLMP-1.