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.

中文翻译：

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LDB1和SWI / SNF复合体参与秀丽隐杆线虫BLIMP1 / PRDM1的转录激活和抑制。

BLIMP1 / PRDM1家族的转录因子是重要的发育调节因子。BLIMP1 / PRDM1既可以激活也可以抑制基因表达，但是，激活的机制尚不清楚。因此，我们寻找与秀丽隐杆线虫BLMP-1（BLIMP1 / PRDM1的直系同源物）的基因激活有关的因素。BLMP-1激活bed-3的表达，bed-3是涉及外阴发育的基因。通过筛选在外阴发育中起作用的核蛋白，我们确定了BLMP-1依赖bed-3表达所需的两种蛋白（LDB-1和HAM-3）。LDB-1是LIM结合蛋白（LDB）家族的唯一秀丽隐杆线虫成员，而HAM-3是SWI / SNF复合物（人SMARCD3 / BAF60C的直系同源物）的辅助亚基。还涉及核心的SWI / SNF亚基SWSN-1（人SMARCC1 / BAF155的直系同源物）。我们发现LDB-1和HAM-3绑定到BLMP-1，这表明BLMP-1募集了LDB-1和SWI / SNF复合体以激活bed-3表达。有趣的是，LDB-1和HAM-3参与转录激活和抑制。特别地，BLMP-1，LDB-1和HAM-3共同调节一组皮下基因，包括bed-3（激活），col-124（激活）和lin-29（抑制）。另一方面，LDB-1和HAM-3不需要激活或抑制BLMP-1调控的某些基因（例如T09D3.8，nas-10）。我们还发现，人LDB1，SMARCD3 / BAF60C和SMARCC1 / BAF155在体外均与人BLIMP1 / PRDM1物理相互作用，并在体内与BLIMP1 / PRDM1密切相关。综上所述，这些结果确定LDB1和SWI / SNF是BLIMP1 / PRDM1的保守保守因子，