DBL-1/BMP signaling pathway Smads and master transcription regulator BLMP-1/PRDM1 interact to regulate organismal traits in Caenorhabditis elegans

Transforming Growth Factor beta (TGF-{beta}) signaling plays a crucial role in regulating various organismal traits in animals through the activation of Smad transcription factors. However, the precise mechanisms by which these Smads control gene expression to generate diverse traits remain unclear. In order to investigate this, we employed the Caenorhabditis elegans model organism to identify a master chromatin remodeler, B-lymphocyte maturation protein-1 (BLMP-1, a protein homologous to human PRDM1/BLIMP1), as a crucial partner in Smad-mediated gene expression regulation.

Previous studies have demonstrated that BLMP-1/PRDM1 influences organismal traits that are also affected by the C. elegans TGF-{beta} superfamily member DBL-1. We discovered genetic interactions between the DBL-1 pathway and the blmp-1 gene, suggesting that these two pathways interact to regulate various traits. Our findings indicate that BLMP-1/PRDM1 and DBL-1 pathway signaling exhibit an additive effect on body size.

Moreover, blmp-1 mutants exhibited epistatic relationships with DBL-1 pathway mutants for traits such as male tail development, hermaphrodite gonad development, brood size, lipid levels, movement, and survival. We demonstrated that DBL-1 signaling transcriptionally regulates blmp-1 expression. Furthermore, through yeast-two hybrid analyses, we identified a physical interaction between the DBL-1 pathway Smads and BLMP-1/PRDM1.

Bioinformatics and quantitative PCR analysis revealed that Smads and BLMP-1/PRDM1 regulate the expression of common downstream target genes. Our research unveils novel interactions between the DBL-1 signaling pathway and the BLMP-1 transcription factor, two conserved major regulators, which collectively impact a wide range of organismal traits.

We propose a model in which BLMP-1/PRDM1 functions as a chromatin gatekeeper, modulating the chromatin architecture to control the access of the Smad complex to target genes. Overall, our findings establish a direct link between the TGF-{beta} signaling pathway and the PRDM1-family master transcription regulator, shedding light on the intricate mechanisms by which these elements interact to control larval and adult traits.

Our study provides insights into a conserved mechanism of transcriptional control of developmental traits mediated by the Smad-PRDM axis.