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SUMMARY:Structure meets function at the mouse X chromosome inactivation ce
 nter - Giorgetti\, L (Institut Curie\, Paris)
DTSTART:20120903T142000Z
DTEND:20120903T144000Z
UID:TALK39495@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:Characterizing the folding principles of mammalian chromosomes
  is of capital importance to understand the complexity of gene expression 
 regulation\, particularly during the major transcriptional changes occurri
 ng in development. This may help elucidating the mechanisms by which regul
 atory elements contact gene promoters (i.e. by looping out intervening DNA
 )\, understand what is the cell-to-cell variability of these interactions 
 and how it does reflect transcriptional variability. We analyzed a 4.5 Mb 
 region of the X chromosome that includes the X-inactivation center by Chro
 matin Conformation Capture Carbon-Copy (5C)\, in order to gain insights in
 to how chromatin structure is organized during early mouse embryonic stem 
 cell (ESC) differentiation. We uncovered that chromatin is organized into 
 Topologically Associating Domains (TADs)\, within which genomic elements p
 referentially interact. To fully reconstruct the statistical repertoire of
  chromatin conformations that give rise to these domains\, we have used a 
 combination of Monte Carlo simulations of a polymer model\, high-resolutio
 n DNA FISH and quantitative RNA FISH. We show that in the TAD that contain
 s the Tsix ncRNA (a master regulator of X-chromosome inactivation)\, enhan
 cer-promoter contacts take place in a subset of cells where the whole doma
 in is compacted\, rather than resulting from stable DNA loops. In these ce
 lls\, the probability of transcribing a gene is higher than in cells where
  the domain is in an elongated conformation. We thus show a correlation be
 tween the spatial proximity of a promoter and an enhancer and their transc
 riptional activity at the single cell level.\n\n
LOCATION:Seminar Room 1\, Newton Institute
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