Gene regulation is controlled by multiple mechanisms that function at levels ranging from genome-wide to gene-specific. Understanding the mechanisms of gene regulation at all levels is important for discerning proper organ development and function as well as interpreting the changes that occur in mutant organs, which lead to defects and diseases. To better understand the mechanisms functioning at different levels of gene regulation in organ development and function, I studied the role of the environment, chromatin remodeling, and gene-specific transcriptional regulation on the C. elegans excretory system, which is similar to mammalian kidneys.
Class III POU-homeobox transcription factors are expressed in the renal organs of species from C. elegans to mammals. However, the functional role for these factors in renal organs is not well characterized. In this dissertation, I studied the role of the C. elegans POU-III transcription factor, CEH-6, in the excretory cell to address this question. I performed molecular and biochemical studies, which show CEH-6 regulates a subset of genes expressed in the excretory cell. This work suggests that a role for POU-III factors in renal organs may be to modulate the expression of functionally related genes.
Chromatin structure also influences the accessibility of transcription factors to target genes, and thereby is important for gene expression. In this study, I show LEX-1 and TAM-1 function to attenuate transgene silencing in somatic tissue by acting regionally as part of a complex that broadly regulates expression of genes in repetitive DNA.
Additionally, environmental cues can play a role in regulating gene expression. Previous work by other labs has shown dauer larvae exhibit an increased osmotic tolerance, suggesting the excretory system may be altered. I was interested in understanding the biological changes responsible so I characterized the excretory system anatomy in dauer larvae. I found an altered morphology and the positional alignment of the excretory duct cell and excretory cell in dauer larvae, which may be related to the increased osmotic tolerance.
Together, the results from these studies support the idea that organisms integrate information from multiple levels and mechanisms of regulation in order to direct their development and function.