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TZID:Europe/Paris
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BEGIN:VEVENT
UID:1-456@lptms.universite-paris-saclay.fr
DTSTART:20161005T110000Z
DTEND:20161005T120000Z
DTSTAMP:20160913T185807Z
URL:http://www.lptms.universite-paris-saclay.fr/seminars/physics-biology-i
 nterface-seminar-daan-noordermeer/
SUMMARY:Physics-Biology interface seminar: Daan Noordermeer - LPTMS\, salle
  201\, 2ème étage\, Bât 100\, Campus d'Orsay - 5 Oct 16 11:00
DESCRIPTION:CTCF mediates allele-specific 3D domain structure at paternally
  imprinted gene loci\nDaan Noordermeer (I2BC\, Gif-sur-Yvette\, France)\nN
 OTE THE NEW LOCATION (due to renovation work at LPS)\n\nImprinted genes ar
 e mammalian genes where only one copy (allele) is active\, depending on wh
 ether it is inherited from the mother or the father. This selective activi
 ty is determined by allele-specific DNA methylation at defined sites in th
 e genome\, so-called Imprinting Control Regions (ICRs). Recent microscopy 
 studies by the group of Robert Feil (IGM-Montpellier\, France) have reveal
 ed that imprinted genes are differently organized in the cell nucleus\, de
 pending on their parental origin (Kota et al.\, 2014). We have used high-r
 esolution 4C-seq studies (Circular Chromosome Conformation Capture) to dis
 sect the mechanisms and dynamics of this differential organization at the 
 Dlk1-Dio3 and Igf2-H19 loci.\n\n\nRecent studies have revealed that mammal
 ian genomes are organized into Topologically Associating Domains (TADs) th
 at demarcate ‘gene regulatory neighborhoods’ (Dixon et al.\, 2012). Th
 ese physical domains are formed through a mechanism of ‘loop extrusion
 ’ of the DNA fiber\, with borders that are demarcated by opposing bindin
 g sites of the architectural CTCF protein (Fudenberg et al.\, 2016). I wil
 l show that the imprinted Dlk1-Dio3 and Igf2-H19 loci are organized into d
 ifferent DNA domains\, determined by allele specific CTCF binding.\n\n\nBo
 th the Dlk1-Dio3 and Igf2-H19 loci are contained within large\, invariant 
 Topologically Associating Domains (TADs). The presence of the CTCF protein
  at the unmethylated ICRs on the maternal allele allows the establishment 
 of new loops within the TADs. This result in the formation of a domain tha
 t acts like a cage\, thereby shielding regulatory elements from nearby gen
 es. \n\n\nAt the paternal alleles\, DNA methylation at the ICR inhibits CT
 CF binding. As a result\, the paternal Igf2-H19 allele displays little spe
 cific organization within the TAD. In contrast\, at the paternal Dlk1-Dio3
  locus\, loops are formed between more distant unmethylated CTCF sites. Th
 e paternal allele therefore forms a much larger subdomain that is containe
 d within the TAD.\n\n\nOur work\, for the first time\, shows that constitu
 tive TADs can have a markedly different allele-specific internal domain or
 ganization. Moreover\, it shows that methylation-dependent DNA binding of 
 the CTCF protein at ICRs guides the process of loop extrusion\, thereby ch
 ange the 3D structure of chromatin domains. We speculate that the imprinte
 d patterns of gene expression at these loci are mostly imposed by the mate
 rnal 3D architecture\, supporting previous genetic studies.\n
CATEGORIES:physbio,seminars
LOCATION:LPTMS\, salle 201\, 2ème étage\, Bât 100\, Campus d'Orsay\, 15 
 Rue Georges Clemenceau\, Orsay\, 91405\, France
GEO:48.698185;2.181768
X-APPLE-STRUCTURED-LOCATION;VALUE=URI;X-ADDRESS=15 Rue Georges Clemenceau\,
  Orsay\, 91405\, France;X-APPLE-RADIUS=100;X-TITLE=LPTMS\, salle 201\, 2è
 me étage\, Bât 100\, Campus d'Orsay:geo:48.698185,2.181768
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