Advisor(s)

Nicole Riddle

Committee Member(s)

Farah Lubin
Igor Chesnokov
Melissa Harris

Document Type

Thesis

Date of Award

6-18-2026

Degree Name

Master of Science (MS)

School

College of Arts and Sciences

Department

Biology

Abstract

Heterochromatin Protein 1 (HP1) family members are highly conserved, non-histone chromosomal proteins essential for heterochromatin formation and transcriptional regulation. In Drosophila melanogaster, HP1a functions both as a transcriptional repressor and activator, as well as other functions, and undergoes post-translational modifications, including phosphorylation. The functional consequences of HP1a phosphorylation remain largely unexplored. This thesis investigates the role of phosphorylation at serines 89/90/91 (S899091) of HP1a by generating two mutant alleles: a phospho-mimic (SE) and a phospho-block (SA). Both alleles produce stable mRNA transcripts; however, Western blot analysis revealed reduced protein accumulation relative to wildtype HP1a. Homozygous phospho-block animals are embryonic lethal across both genetic backgrounds tested, whereas homozygous phospho-mimics are viable through the adult stage. Functional assays demonstrated that both mutant alleles suppress and enhance position effect variegation in a location dependent manner. At the organismal level, homozygous phospho-mimic mutants exhibited reduced fertility and smaller gonads in both sexes, but only in a mixed genetic background, pointing to context dependent effects in the germline. Behavioral assays further revealed increased activity in young mutant males and homozygous phospho-mimic females, a phenotype absent in older animals. Lifespan analyses uncovered sex and allele specific outcomes: all mutant females lived longer than wildtype, heterozygous phospho-mimic males showed extended lifespan, while heterozygous phospho-block males displayed reduced longevity. Together, these findings demonstrate that altering HP1a phosphorylation at S899091 disrupts protein accumulation, impacts transcriptional regulation, and leads to diverse organismal phenotypes. These results suggest that phosphorylation at S899091 modulates HP1a protein stability and function, with specific roles in the germline that depend on genetic background. More broadly, this work highlights the significance of post-translational modifications in regulating chromatin proteins and their contributions to organismal health.

Keywords

Drosophila melanogaster;Heterochromatin;HP1a;Multifunctionality;Phosphorylation

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