A transcriptional cofactor regulatory network for the C. elegans intestine

Abstract

Chromatin modifiers and transcriptional cofactors (collectively referred to as CFs) work with DNA-binding transcription factors (TFs) to regulate gene expression. In multicellular eukaryotes, distinct tissues each execute their own gene expression program for accurate differentiation and subsequent functionality. While the function of TFs in differential gene expression has been studied in detail in many systems, the contribution of CFs has remained less explored. Here, we uncovered the contributions of CFs to gene regulation in the Caenorhabditis elegans intestine. We first annotated 366 CFs encoded by the C. elegans genome and assembled a library of 335 RNAi clones. Using this library, we analyzed the effects of individually depleting these CFs on the expression of 19 fluorescent transcriptional reporters in the intestine and identified 216 regulatory interactions. We found that different CFs regulate different promoters, and that both essential and intestinally expressed CFs have the greatest effects on promoter activity. We did not find all members of CF complexes acting on the same set of reporters but instead found diversity in the promoter targets of each complex component. Finally, we found that previously identified activation mechanisms for the acdh-1 promoter use different CFs and TFs. Overall, we demonstrate that CFs function specifically rather than ubiquitously at intestinal promoters and provide an RNAi resource for reverse genetic screens.

TheC. elegansMyc-family of transcription factors coordinate a dynamic adaptive response to dietary restriction

“…In agreement with our Gene Ontology analysis of eat-2 expression changes, we found a substantial and significant set of downregulated genes in eat-2 mutant animals to be enriched in sperm, as well as significant over-representation of muscle-associated genes. The intestine is commonly referred to as the most metabolically active tissue in C. elegans, and both the MML-1::MXL-2 complex and PHA-4 act in intestinal cells in adult animals (Panowski et al 2007;Johnson et al 2014;Nakamura et al 2016;Horowitz et al 2023); we found enrichment for intestinally expressed genes in both the up-and down-regulated transcriptional response to eat-2, mxl-2, or pha-4 single-perturbation conditions. Intriguingly, we found enrichment of neuron-associated genes among those down-regulated in mxl-2 null mutant animals, which suggests Myc-family TFs may coordinate organismal adaptive responses from the nervous system.…”