Abstract

The chromatin landscape of Drosophila: Heterochromatin differences between species, sexes, and ages

By

Emily Jordan Brown

Doctor of Philosophy in Integrative Biology

University of California, Berkeley

Professor Doris Bachtrog, Chair

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, and can be most broadly characterized by the gene-rich and repeat-poor euchromatin and the gene-poor and repeat-rich heterochromatin. Genome-wide profiling of chromatin components provides a method of generating a functional annotation of the underlying DNA sequences, as groups of correlated histone modifications are associated with both euchromatin and heterochromatin, as well as more specific functions such as active transcription or polycomb-mediated repression. Although there has been much progress towards understanding the general hallmarks of different chromatin functions, there have been many fewer efforts to characterize on a broad scale how different types of chromatin differ between species, sexes, or individuals of different ages.

In this dissertation, I investigate whether differences in sex chromosome content contributes to genome-wide differences in the chromatin landscape across species with different numbers of X chromosomes, between males and females, and between old and young individuals. Sex chromosomes have a unique chromatin structure compared to autosomes. The single male X chromosome recruits the dosage compensation complex and becomes hyper-acetylated, resulting in an approximate 2-fold increase of transcription. Females, however, have two copies of the X chromosome and do not recruit the dosage compensation complex to the X chromosome. In contrast to the hyper-transcription of the X chromosome in males, the male-limited Y chromosome is transcriptionally silenced via heterochromatin formation, as it is gene-poor and repeat-rich.

The Drosophila Y chromosome is known to harbor variation that effects position effect variegation (the ability of spreading heterochromatin to induce partial silencing of reporter genes in some cells, resulting in mosaic expression patterns). However, previous studies have not assayed the Y chromosome’s effect on heterochromatin integrity genome-wide, nor have they directly assayed the role of the Y chromosome in generating differences in heterochromatin composition observed between males and females. Here, I use genome-wide profiles of heterochromatic histone modifications in XO and XYY males, and XXY females, to assess the effect of the Y chromosome on genome-wide heterochromatin.

The chronic deterioration of chromatin structure has been implicated in aging, and an overall loss of heterochromatin has been observed in many old animals. Males and females differ in both their average lifespan as well as their total amount of heterochromatic sequences, due to the presence of the large heterochromatic Y chromosome in males. I compare lifespans, genome-wide heterochromatin profiles, and expression of repetitive elements during aging in males and females, as well as XO and XYY males, and XXY females, to interrogate whether the Y chromosome contributes to differences in lifespan and loss of chromatin organization between the sexes.