Abstract

Modulation of multiple levels of chromatin structure has an important role in gene activation. Promoters and enhancers are typically described as being depleted of nucleosomes, and as associated with histone H3 acetylation. At a larger scale, enhancers in the mammalian genome can control their target genes over very large genomic distances, and across intervening genes. The sculpting of three-dimensional chromosome organization, especially that brought about through cohesin-dependent loop extrusion and the formation of topologically associating domains (TADs), is thought to be important for facilitating and constraining the action of enhancers. Addressing these two levels of chromatin organization, I will first describe our analysis of acetylated H3 lysine 115 (H3K115ac), a residue on the lateral surface at the nucleosome dyad, that we find associated with “fragile” nucleosomes at promoters and enhancers. I will then discuss our work, using synthetic transcriptional activators, that examines how enhancers can communicate with promoters across large linear genomic distances in the context of topologically associating domains formed by cohesin-mediated loop extrusion and transcriptional hubs.

About Wendy Bickmore

Wendy Bickmore is Director of the MRC Human Genetics Unit at the University of Edinburgh. Her undergraduate degree is in Biochemistry from the University of Oxford, and she then completed a PhD in Molecular Biology at the University of Edinburgh. Following a postdoc in human genetics, Wendy started her independent research group as a fellow of the Lister Institute for Preventive Medicine. She is fascinated by the three-dimensional organization of the human genome in cells and how that influences genome function in health and disease. Her current research explores how the non-coding genome regulates gene expression including how distant enhancers communicate with their target gene promoters. Wendy is a Fellow of the Royal Society, the Royal Society of Edinburgh and of the Academy of Medical Sciences, a member of the European Molecular Biology Organization and an international member of the National Academy of Sciences. She was awarded a CBE for service to science and to women in science.

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