All ETDs from UAB

Advisory Committee Chair

Nicole Riddle

Advisory Committee Members

Malay Basu

Melissa Harris

Farah Lubin

Tatiana Marquez-Lago

Trygve Tollefsbol

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

The Heterochromatin Protein 1 (HP1) family are a group of non-histone chromosomal proteins with functions in many essential DNA processes. The HP1 family is highly conserved, and many eukaryotic genomes contain multiple HP1 genes. Individual paralogs specialize in specific functions, although they do have overlapping roles in some processes. In Drosophila, there are three HP1 paralogs expressed in somatic cells: HP1a, HP1B and HP1C. All three of these proteins have previously been implicated in both the positive and negative regulation of transcription. Furthermore, the three proteins share binding sites and colocalize broadly throughout the Drosophila genome. Here, we investigate individual contributions of HP1 paralogs to the regulation of gene expression at Drosophila transcription start sites. First, we review the existing literature on the roles of HP1 orthologs in transcriptional regulation, emphasizing the Drosophila HP1 family as a model. We outline the evolutionary history of the HP1 family and examine functional specialization of HP1 orthologs in several fungal, plant and animal genomes. We next perform an integrated analysis of epigenomic and transcriptomic data in multiple Drosophila cell types. Through this analysis, we find that HP1 proteins share a majority of their binding sites at genes and that simultaneous binding of multiple HP1 proteins is indicative of higher overall gene expression. Depletion of individual HP1 proteins perturbs expression of their binding targets through disruptions to RNA polymerase II activity. Finally, we use a machine learning approach to infer individual functions of HP1 proteins iii in transcription regulation through elastic net regression, and validate these predictions using CRISPR/dCas9. Overall, our work highlights the importance of considering how interactions between HP1 paralogs are coordinated to regulate transcriptional outcomes of Drosophila genes.

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