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Monday, December 17th, 2018
Centre de Recherche - Paris - Amphithéâtre Hélène Martel-Massignac

Regulation of Replication Timing and Chromosome Architecture

The temporal order of DNA replication (replication timing, RT) is highly coupled with genome architecture, but cis-elements regulating spatio-temporal control of replication have remained elusive. We performed an extensive series of CRISPR mediated deletions and inversions and high-resolution capture Hi-C of a pluripotency associated domain (DppA2/4) in mouse embryonic stem cells. Whereas CTCF mediated loops and chromatin domain boundaries were dispensable, deletion of three intra-domain prominent CTCF-independent 3D contact sites caused a domain-wide delay in RT, shift in sub-nuclear chromatin compartment and loss of transcriptional activity, These “early replication control elements” (ERCEs) display prominent chromatin features resembling enhancers/promoters and individual and pair-wise deletions of the ERCEs confirmed their partial redundancy and interdependency in controlling domain-wide RT and transcription. Our results demonstrate that discrete cis-regulatory elements mediate domain-wide RT, chromatin compartmentalization, and transcription, representing a major advance in dissecting the relationship between genome structure and function. 

Event poster



Florida State University

Invited by

Dr. Geneviève Almouzni
Domain 2 - UMR 3664 - Nuclear Dynamics

Institut Curie

Dr. Chunlong Chen
Domain 2 - UMR 3244 - Dynamics of genetic Information

Institut Curie


Mrs. Olivia LANDRE


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