; IGBMC (Institute of Genetics and Molecular and Cellular Biology), Strasbourg, France
MSCi University of Cambridge 2000-2004, PhD 海角社区论坛 (Peter Fraser) 2004-2008 Postdoc, IGH (Institute of Human Genetics), Montpellier, France 2008-2014 Principal Investigator, IGBMC 2014-present
Sophisticated control of gene expression programs during development is brought about by enhancers, elements which can activate target promoters over large genomic distances. Despite great progress in identify and characterizing enhancers, it is still not clear how exactly they regulate transcription with such specificity. Chromatin conformation capture experiments suggest that enhancers physically contact their regulated genes via 鈥渓ooping鈥 interactions, but recent microscopy experiments raise questions over this simple model. Using the pluripotency gene Sox2, and its embryonic stem cell-specific enhancer, the SCR, as a model locus, we have uncovered different aspects of the spatiotemporal regulation of gene expression. In the first case, we find a surprising decoupling between aspects of the enhancer that are responsible for 鈥渋nteractions鈥 and those that are necessary for transcriptional activation. In the second case, when tracking the promoter and enhancer in living cells, we find that their inherent mobilities are specifically matched when the gene is being transcribed. Overall, these results are consistent with a model whereby transcription is spatially coordinated in specialized nuclear microenvironments to facilitate distal regulation.
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