Bonjour à tous, toutes, [🇬🇧 english below]
C’est avec grand plaisir que je vous informe que nous aurons le plaisir d’accueillir le Dr Ramy Ragheb pour un séminaire externe le vendredi 26 juin 2026 à 11h30.
Pour celles et ceux qui ne le connaissent pas, Ramy a été doctorant au laboratoire de 2012 à 2016.
Après un postdoctorat à Cambridge de 2017 à 2025, il est aujourd’hui Research Associate à l’Université d’Exeter.
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Hello everyone,
It is my pleasure to announce that we will host an external seminar by Dr. Ramy Ragheb on Friday, June 26, 2026, at 11:30 AM.
For those who may not know him, Ramy was a PhD student in our laboratory from 2012 to 2016.
After completing a postdoctoral position in Cambridge from 2017 to 2025, he is now a Research Associate at the University of Exeter.
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Title: Enhancer Resetting: a two-phase model of signal-responsive regulation
Short abstract: How cells generate transcriptional responses to signalling from a shared chromatin template remains poorly understood. We have shown that ERK activation in mouse embryonic stem cells triggers rapid, NuRD-dependent destabilisation of transcription factor binding and chromatin structure at active enhancers, followed by selective re-stabilisation through a switch in transcription factor occupancy - a phenomenon we term Enhancer Resetting.
Full Abstract: During development, cellular identity is ultimately determined by transcriptional output: lineage-specific genes must be activated, while genes associated with alternative fates must be repressed. This process depends on the activity of chromatin remodelling complexes, which regulate the
accessibility of transcription factors to chromatin regulatory elements. In addition, cellular identity is shaped by exposure to intercellular signals. Understanding the mechanisms by which extracellular signals are translated into changes in the transcriptional program is essential for understanding cell fate decisions during development, as well as in disease conditions such as cancer. Here we describe a rapid and widespread enhancer resetting event in response to ERK signalling in mouse ES cells. This process occurs in two distinct phases: an immediate, genome-wide alteration in transcription factor binding dynamics at regulatory regions which is dependent on the release of paused RNA Polymerase II, followed by the re-establishment of a context appropriate, stable chromatin state. We demonstrate that the chromatin remodelling complex NuRD is required for this reestablishment phase and for the appropriate transcriptional response to ERK signalling. We propose that enhancer resetting places genomic regulatory regions in a state which is permissive to the exchange of transcription factors in order to establish a new, stable enhancer topology enabling rapid yet precise transcriptional response to extracellular signals.