Authors: John Schoelz 1,2; Annesha King 1,2; Nicole Riddle 1,2
Affiliations: 1) University of Alabama-Birmingham; 2) Department of Biology
Keywords: c. activators/coactivators; d. repressors/corepressors
Heterochromatin Protein 1 (HP1) was discovered inDrosophila and is a major component of heterochromatin. In Drosophila melanogaster, there arethree somatically expressed HP1 proteins: HP1a, HP1b, and HP1c. HP1a is essential in flies and is necessary for genomic integrity. While enriched in heterochromatin, it has binding targets in heterochromatin and euchromatin and it acts as both a repressor and activator of gene expression. HP1b is found in heterochromatin and euchromatin as well and acts as repressor and activator of gene expression depending on the target. HP1c is found in both chromatin compartments as well, but its function seems to be mostly in gene activation. Thus, all three proteins are involved in the regulation of gene expression, and analysis of ChIP-seq data suggests that they share many binding sites. To understand the contribution of the HP1 proteins to gene regulation, elastic net regression models were utilized. In this study, we assessed gene expression changes by recruiting HP1 proteins to endogenous genes. These models suggest that HP1b is of particular importance, but that genomic features including promoter motifs, accessibility, and sequence composition also contribute. To address the model predictions, we used dCas9 to recruit HP1 proteins to specific targets in the genome. We found that dCas9 tethered HP1 proteins have different transcriptional outcomes depending on gene target.