Chromatin Folding and Gene Activation - From the Nucleosome to Transcription Hubs

Explore the intricate mechanisms of chromatin structure and gene regulation in this comprehensive lecture by Wendy Bickmore, Director of the MRC Human Genetics Unit at the University of Edinburgh. Delve into the multiple levels of chromatin organization that play crucial roles in gene activation, from the molecular level of nucleosomes to the formation of transcriptional hubs. Examine how promoters and enhancers are characterized by nucleosome depletion and histone H3 acetylation, and discover the significance of acetylated H3 lysine 115 (H3K115ac) in creating "fragile" nucleosomes at these regulatory regions. Investigate the complex three-dimensional chromosome organization, particularly focusing on cohesin-dependent loop extrusion and the formation of topologically associating domains (TADs) that facilitate and constrain enhancer function. Learn how enhancers can control target genes across vast genomic distances and intervening genes through sophisticated communication mechanisms. Understand the research findings on synthetic transcriptional activators and their role in demonstrating enhancer-promoter communication within the context of TADs formed by cohesin-mediated loop extrusion. Gain insights into the cutting-edge research on genome organization and its implications for understanding gene regulation in health and disease from one of the leading experts in the field.