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Apr 25, 2022
From 11:30 AM to 12:30 PM


Karen Adelman

Karen Adelman

Mammalian SWI/SNF globally activates both genes and enhancers

Karen Adelman PhD
Professor of Biological Chemistry and Molecular Pharmacology
Harvard Medical School
Boston, MA, USA

This conference is organized by François Robert. It is part of the 2021-2022 IRCM conference calendar.

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

Zoom Link :
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 the conference:
SWI/SNF chromatin remodeling complexes move and reorganize nucleosomes at gene promoters and enhancers to modulate access to DNA. Although SWI/SNF subunits are commonly mutated in disease, how SWI/SNF impacts gene expression remains unclear, limiting therapeutic options. Long-term depletion studies have reached conflicting conclusions regarding the scope and consequences of SWI/SNF remodeling; while some suggest a positive role for SWI/SNF at subsets of genes or enhancers, others implicate SWI/SNF in repression. Here, we use a fast-acting catalytic inhibitor of SWI/SNF remodeling, to elucidate the direct targets and effects of SWI/SNF. SWI/SNF inhibition rapidly causes global loss of chromatin accessibility at promoters and enhancers, concomitant with widespread suppression of transcription initiation. Notably, many promoters can reactivate in the absence of SWI/SNF remodeling via EP400/TIP60-mediated compensation. In contrast, a set of promoters and most enhancers fail to recover accessibility or transcription activity. Importantly, molecular characteristics defining SWI/SNF-dependence at these loci can predict sensitivity to SWI/SNF inhibition in cancer cells. Together, our findings demonstrate a universal role for SWI/SNF in generating accessible chromatin that is masked by compensation during long-term SWI/SNF disruption. Further, reestablishment of promoter activity in the absence of enhancer recovery implies disruption of promoter-enhancer communication upon SWI/SNF perturbation, providing insights into disease. 

About Karen Adelman:
Dr. Karen Adelman is a Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School (Boston, MA, USA), where she founded the Nascent Transcriptomics Core. Her research aims to characterize the interplay between gene expression and cellular signaling, chromatin architecture and genome epigenetic features, using a combination of functional genomics, genetics and biochemistry. Her contributions to literature include major discoveries by her team and via collaborative work, most of which were published in top peer-reviewed journals (Nature, Science, Blood, Molecular Cell, etc.). Dr. Adelman is dedicated to supporting women and trainees from groups that are under-represented in science: she is an Advisor and Mentor in several networks at Harvard and Harvard Medical School, namely Women in Science and Engineering (WiSE) and Female Leaders in Science (FLIS).

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