UC Berkeley

Abstract

Nucleosome Occupancy and Modification in C. elegans Dosage Compensation

By

Christine Gail Preston

Doctor of Philosophy in Molecular and Cell Biology

University of California, Berkeley

Professor Barbara J. Meyer, Chair

Species with sex-determining chromosomes have also evolved sex chromosome dosage compensation, a process equalizing the sex chromosome gene expression of males (1X) to that of the females (2X). Dosage compensation strategies in well-studied model organisms evolved independently, however certain themes are constant between the different systems. Chromatin modifications are key components of dosage compensated X chromosomes in Drosophila and mammals, and recent reports have independently implicated the histone 4 lysine 20 monomethy mark, and nucleosome occupancy at X-chromosome promoters as playing roles in C. elegans dosage compensation. Here I report important advances in our understanding of the role of chromatin in C. elegans dosage compensation and general biological processes.

In chapter 2, I report our findings into the role of the H4K20 histone methyl transferase, set-1, in C. elegans. H4K20me1 is a histone modification associated with a wide variety of cellular functions, including condensed chromatin and transcriptional regulation. H4K20me1 is enriched on the dosage compensated X chromosomes in XX hermaphrodites, and this enrichment has been proposed to play an integral role in dosage compensation in worms. Here I report work that shows the major role of H4K20me1 in C. elegans is not X-chromosome dosage compensation, and instead that the mark is playing important roles in non-sex-specific functions, including the regulation of gene expression on all chromosomes.

In chapter 3, I report findings about the underlying mononucleosome structure at transcriptional start sites as well as DCC binding sites. I show that, similar to the situation at human promoters, C. elegans promoters have high, DNA-specified nucleosome occupancy covering promoter regions. These active promoters are remodeled in vivo, and the majority of the promoters consist of a canonical active promoter formation, with a nucleosome depleted region (NDR) upstream of the TSS, and well positioned nucleosome arrays emanating in either direction from the NDR. I also report that, in contrast to previous reports, promoters on the X chromosome are not uniquely higher in nucleosome occupancy; which had previously been postulated to be related to X-specific repression in somatic, sex-specific chromosome dosage compensation and in germline silencing.