LDB1 and the SWI/SNF complex participate in both transcriptional activation and repression by Caenorhabditis elegans BLIMP1/PRDM1

Abstract

Transcription factors of the BLIMP1/PRDM1 family are important regulators of development. BLIMP1/PRDM1 can both activate and repress gene expression, however, the mechanism of activation is not well understood. Therefore, we looked for factors involved in gene activation by C. elegans BLMP-1, the ortholog of BLIMP1/PRDM1. BLMP-1 activates the expression of bed-3, a gene involved in vulval development. By screening nuclear proteins that function in vulval development, we identified two proteins (LDB-1 and HAM-3) required for BLMP-1 dependent bed-3 expression. LDB-1 is the sole C. elegans member of the LIM Binding Protein (LDB) family, whereas HAM-3 is an accessory subunit of the SWI/SNF complex (ortholog of human SMARCD3/BAF60C). A core SWI/SNF subunit SWSN-1 (ortholog of human SMARCC1/BAF155) is also involved. We found that LDB-1 and HAM-3 bind to BLMP-1, suggesting that BLMP-1 recruits LDB-1 and the SWI/SNF complex to activate bed-3 expression. Interestingly, LDB-1 and HAM-3 are involved in both transcriptional activation and repression. In particular, BLMP-1, LDB-1 and HAM-3 co-regulate a set of hypodermal genes including bed-3 (activated), col-124 (activated) and lin-29 (repressed). On the other hand, LDB-1 and HAM-3 are not required for activation or repression of some genes regulated by BLMP-1 (e.g. T09D3.8, nas-10). We also found that human LDB1, SMARCD3/BAF60C and SMARCC1/BAF155 all physically interact with human BLIMP1/PRDM1 in vitro and are closely associated with BLIMP1/PRDM1 in vivo. Taken together, these results identify LDB1 and SWI/SNF as likely conserved cofactors of BLIMP1/PRDM1, which participate in activation and repression of a subset of BLIMP1/PRDM1-regulated genes.

Keywords: BLIMP1; Caenorhabditis elegans; PRDM1; Transcriptional regulation.