493C Poster - 06. Regulation of gene expression
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Michael Rogers ¹; Coralie Drelon ¹; Helen Belalcazar ¹; Owen Marshall ²; Julie Secombe ¹

Affiliations:
1) Albert Einstein College of Medicine, Bronx, NY; 2) Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia

Keywords:
j. epigenetics; d. histone variants and modifications

Chromatin-regulating proteins are powerful supervisors of the genome that are critical for the precise control of gene expression. Developmental processes depend on these proteins for the coordinated regulation of transcriptional programs that are essential for proper tissue formation and organismal maturation. However, there still exists significant gaps in knowledge about the mechanisms of this fine-tuning aspect of gene expression, and tissues like the prothoracic gland provide fantastic settings to dissect these dynamics during development. Here we show that lysine demethylase 5 (KDM5, formerly Lid), a histone modifier capable of dynamically regulating chromatin through multiple functions, plays critical roles in the prothoracic gland. Interestingly, animals lacking canonical KDM5 histone demethylase activity are viable, but kdm5 null mutants exhibit delayed development and a failure to eclose after metamorphosis. Although KDM5 is ubiquitously expressed across the organism throughout development, we have demonstrated that restoring KDM5 expression specifically within the prothoracic gland of kdm5 null mutant animals rescues both the larval developmental delay and pupal lethality. Our studies show that KDM5 regulates MAPK signaling within prothoracic gland cells that functions in promoting endoreplication and ecdysone hormone production. Leveraging Targeted DamID technology, we have generated the first genomic-binding data set (akin to ChIP-seq) for prothoracic gland cells and identified the genomic targets of KDM5 localization across the genome. We are currently integrating these data with transcriptome, interactome, and cellular analyses to characterize KDM5-mediated mechanisms of gene expression regulation in these cells. Taken together, our studies provide key insights into the chromatin regulation critical to prothoracic gland function as well as expand our understanding of the functions of the transcriptional regulators like KDM5 that coordinate development.