Transcriptional regulation plays a major role in gene expression, and is critical for development and diseases. To understand the molecular mechanisms of transcriptional control, I took advantage of the classic gene regulation model, Drosophila melanogaster, and developed approaches from both a genome wide angle and zooming in to the specific gene. On the genome level, I carried out genome-wide studies to characterize binding profiles for Drosophila retinoblastoma family proteins. I identified novel, yet conserved roles for retinoblastoma proteins in regulation of signaling pathways and ribosomal biosynthesis. I discovered that the retinoblastoma cofactors might be an important regulator of cellular growth through control of ribosomal gene expression, an unrecognized feature of this tumor suppressor protein that is apparently evolutionarily conserved in mammals. On the specific gene level, I characterized the cis-regulatory landscape of the Drosophila insulin receptor gene, a gene that is frequently involved in many diseases such as diabetes, Alzheimer’s, and cancer. I identified many dynamically and redundantly regulated enhancers embedded in the large insulin receptor gene locus, and demonstrated that a “housekeeping” gene can be subject to control by extraordinarily complex regulatory circuitry.
Read
