Chromatin accessibility and the dynamic control of genome expression

Carl Wu, PhD
Bloomberg Distinguised Professor
Department of Biology
Johns Hopkins University
Baltimore, MD, USA
Carl Wu Laboratory

This conference is hosted by François Robert, PhD. The title and the abstract will be available soon. This conference is part of the 2022-2023 IRCM conference calendar.

In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal
Wearing a mask is mandatory at all times

Online:
Zoom Link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

About this conference: 
Gene expression control is accomplished through sequence-specific transcription factors (TFs), but how these proteins establish and maintain epigenetic landscapes in the face of dynamic nucleosome competition is poorly understood. To study this competition in real time our laboratory uses super-resolution fluorescence microscopy to image the single-molecule dynamics of major transcription proteins and ATP-driven chromatin remodeling enzymes in living cells. We find that remodelers as a family bind to chromatin transiently but frequently with dwell times of several seconds in vivo, consistent with in vitro time measurements of nucleosome sliding and histone exchange. Together with reported changes in nucleosome positioning genome-wide on conditional remodeler depletion, our results suggest that promoters and enhancers are subject to dynamic expansion and contraction of nucleosome-depleted regions (NDRs) on a timescale of seconds. To regulate nucleosome dynamics at regulatory DNA elements, ‘pioneer’ TFs such as yeast General Regulatory Factors Reb1 and ABF1, and Drosophila GAGA factor/Trithorax-like (GAF) persist on genomic targets with very high occupancy for extended periods despite on-off dynamics. Moreover, GAF’s recruitment of ISWI and SWI/SNF remodeling enzymes expands NDR lengths for the benefit of neighboring TFs whose access to chromatin is facilitated. The persistence of GAF is due to its autonomous chromatin accessibility, protein abundance, DNA binding, multimerization and intrinsically disordered Q-rich GAF domains, in addition to the local clustering of cognate binding sites. Such kinetic dominance of GAF can pioneer establishment and maintenance of open chromatin throughout Drosophila life, providing a dose- and time-sensitive mechanism that is flexibly responsive to homeostatic, developmental and environmental signals. Such a kinetic mechanism would be upstream of and complementary to chemical modification of DNA and histones that embody semi-stable epigenetic marks to regulate genome expression.

About Carl Wu:
Dr. Carl Wu is a Bloomberg Distinguished Professor in the Department of Biology at John Hopkins University (Baltimore, USA), where he studies the structure and function of chromatin ⎯ the complex of genomic DNA, histones, nonhistone proteins and nuclear RNAs ⎯ as it relates to the control of eukaryotic genome expression for growth, homeostasis, and cell and tissue differentiation. His work, mostly funded by grants from the NIH, has been published in top journals such as Science, Molecular Cell and Nature Communications.

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