Description:

The Simpson Querrey Institute for Epigenetics presents:

Rafal Donczew, PhD

Assistant Professor, Cell Cycle and Cancer Biology Research Program
Oklahoma Medical Research Foundation Cancer 

"Dissect the Silencing and Pathogenic Mechanisms of Retrotransposons in Tissue Regeneration" 

Abstract:

The accurate regulation of transcription is critical for gene expression. Perturbations in transcriptional regulation underlie the emergence and progression of human diseases. Despite rapid advances in understanding how basic transcriptional machinery operates at the level of individual genes, it remains elusive how transcriptional programs are regulated genome-wide through the coordinated action of chromatin dynamics, sequence-specific transcription factors, and transcription coactivators.

Our lab studies conserved mechanisms of transcription in the model organism Saccharomyces cerevisiae (yeast). Yeast has been a driving force behind major findings in molecular biology and remains a powerful model to tackle lingering yet fundamental questions. Our current focus is understanding the roles of coactivator complexes and chromatin readers from the bromodomain and extra-terminal domain (BET) family in transcriptional regulation. BET proteins are important for the transcription of most genes in healthy cells and for sustaining aberrant transcriptional programs that underlie many human diseases. Although BET proteins have been implicated in all steps of gene transcription, from shaping the chromatin environment at enhancers and promoters to processing nascent RNA, the complex roles of BET proteins remain poorly understood. Our recent findings illustrate that the primary role of BET proteins is serving as a hub for interactions with multiple regulatory factors, including coactivator complexes, and highlight a surprisingly small contribution of the bromodomains to genome-wide transcription and BET protein chromatin occupancy. Our results expand current understanding of the complex biology of BET proteins and suggest the mechanisms by which cells can bypass bromodomain inhibition in pathological states.