Understanding Enhancer Role in Transcriptional Response

In genetics, an enhancer is a short (50-1500 bp) region of DNA that can be bound with proteins (activators) to activate transcription of a gene or transcription. Despite their discovery more than 35 years ago, the fundamental principles by which enhancers are activated and regulate their coding gene transcriptional targets in metazoans have remained poorly understood. The molecular mechanisms responsible for orchestrating and integrating genome-wide transcriptional responses to diverse signaling pathways critical for developmental, physiological, and pathological regulation are still widely unknown. The Rosenfeld lab has made an effort to study these molecular mechanisms, focused on previously unsuspected aspects of enhancer function, chromosomal structure, and subnuclear architectural interactions. These strategies, which underlie genome-wide transcriptional responses in the endocrine and central nervous systems and are critical for physiological and behavioral processes in all vertebrates, are orchestrated by the network of genomic enhancers. Our recent findings have substantially altered concepts regarding the roles of noncoding RNAs (ncRNAs), mechanisms of enhancer activation and function, and nuclear architecture as critical aspects of regulated gene expression programs. This work has uncovered unexpected aspects of enhancer function, highlighting their functioning as regulated transcription units in dynamic alterations in nuclear architecture, by specific epigenomic strategies with therapeutic implications for many common diseases. We have studied the role of enhancers in a variety of biological systems: pituitary corticotrope, prostate cancer, breast cancer, and neuronal cells