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SUMMARY:Re-evaluating the roles of cohesin and CTCF in genome folding
DTSTART:20220811T120000
DTEND:20220811T130000
DTSTAMP:20260919T231221Z
UID:9c2c601794a7efad296bba3b084b05d85349a9ea1f0d6cc1897786d7
CATEGORIES:Conferences - Seminars
DESCRIPTION:Antonina Hafner\nBoettiger Lab\, Department of Developmental B
 iology\, Stanford University\nAbstract: \n\nAnimal genomes are organized 
 into topologically associating domains (TADs). TADs are linked to importan
 t biological functions\, including enhancer-mediated transcriptional regul
 ation. How TADs form and what role they play in gene regulation is still w
 idely researched and debated. Here\, we used a microscopy approach\, Optic
 al Reconstruction of Chromatin Architecture (ORCA)\, to measure how cohesi
 n and CTCF organize the genome and the consequences for gene regulation.\n
 \nPrevious work has shown that cohesin and CTCF are essential for TAD form
 ation. However\, despite a similar phenotype of TAD loss upon depletion of
  either protein\, polymer models and experiments propose that cohesin and 
 CTCF play different roles in genome organization. Cohesin is believed to f
 acilitate intra-TAD interactions at the expense of inter-TAD contacts\, wh
 ile CTCF is thought to prevent inter-TAD mixing. Consequently\, this would
  suggest a model where cohesin contributes to enhancer-promoter specificit
 y between TADs while CTCF works to prevent erroneous contacts across TAD b
 oundaries.\n\nOur ORCA data challenges these models. Notably\, we found th
 at cohesin is required for maintaining proximity at the sub-3Mb scale and 
 for decreasing ectopic contacts with more distal regions (>5Mb). CTCF orga
 nizes these loops along an axial/radial axis which favors long-range inter
 actions among CTCF proximal sites and opposes them along distal sites. Our
  data provide a structural understanding of how cohesin and CTCF organize 
 the genome at different genomic scales. Based on these measurements we pro
 pose a revised model of how cohesin and CTCF regulate enhancer-promoter sp
 ecificity.
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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