A Transcriptional Cofactor Regulatory Network in the C. Elegans Intestine

Abstract

Transcription is fundamental to growth, development, and homeostasis of all known organisms. It is imperative that genes are expressed correctly, both in time and in specific tissues. Proper spatiotemporal gene expression is controlled by a combination of regulatory factors: DNA binding transcription factors and transcriptional cofactors and chromatin modifiers. Chromatin modifiers are responsible for rearranging DNA structure to affect local transcription. Other transcriptional cofactors work by binding transcription factors and regulating RNA polymerase activity to regulate transcription. While transcription factors have established roles in activating and repressing specific genes, chromatin modifiers and cofactors also act specifically. In multicellular organisms each tissue has its own unique transcriptional program (gene regulatory network) driven by combinations of transcriptional regulators governing the expression of genes necessary for development and homeostasis. To characterize the transcriptional cofactor gene regulatory network, I performed a screen in the Caenorhabditis elegans intestine. Here, the effects of chromatin modifiers and cofactors on nineteen promoters in the C. elegans intestine are assessed using RNAi knockdowns and a set of transcriptional fluorescent reporters. I find no cofactors are universally required to activate all nineteen transcriptional reporters, but certain cofactor complexes seem to work cooperatively to activate or repress the transcription from specific promoters. I also found that transcription from one promoter, that of acdh-1, uses separate transcription factors but common cofactors depending on the biological perturbation activating its transcription. This study demonstrates that cofactors do not act identically at all promoters, similar to the activities of transcription factors.