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Identification of cis Elements for Spatio-temporal Control of DNA Replication

61 Pages Posted: 8 Jun 2018 Publication Status: Published

See all articles by Jiao Sima

Jiao Sima

Florida State University - Department of Biological Science

Abhijit Chakraborty

La Jolla Institute for Allergy and Immunology (LIAI)

Vishnu Dileep

Florida State University - Department of Biological Science

Marco Michalski

The Babraham Institute - Nuclear Dynamics Program

Juan Carlos Rivera-Mulia

Florida State University - Department of Biological Science

Claudia Trevilla-Garcia

Florida State University - Department of Biological Science

Kyle N. Klein

Florida State University - Department of Biological Science

Daniel Bartlett

Florida State University - Department of Biological Science

Brian K. Washburn

Florida State University - Department of Biological Science

Michelle T. Paulsen

University of Michigan at Ann Arbor - Department of Pathology; University of Michigan at Ann Arbor - Department of Environmental Health Sciences; University of Michigan at Ann Arbor - Center for RNA Biomedicine

Daniel Vera

Florida State University - Center for Genomics and Personalized Medicine

Elphège P. Nora

University of California, San Francisco (UCSF) - Gladstone Institute of Cardiovascular Disease; University of California, San Francisco (UCSF) - Roddenberry Center for Stem Cell Biology and Medicine; University of California, San Francisco (UCSF) - Department of Pediatrics; University of California, San Francisco (UCSF) - Cardiovascular Research Institute

Katerina Kraft

Max Planck Society for the Advancement of the Sciences - Rearch Group Development & Disease; Charité - Universitätsmedizin Berlin - Institute for Medical and Human Genetics

Stefan Mundlos

Max Planck Society for the Advancement of the Sciences - Rearch Group Development & Disease; Charité - Universitätsmedizin Berlin - Institute for Medical and Human Genetics

Benoit G. Bruneau

University of California, San Francisco (UCSF) - Gladstone Institute of Cardiovascular Disease; University of California, San Francisco (UCSF) - Roddenberry Center for Stem Cell Biology and Medicine; University of California, San Francisco (UCSF) - Department of Pediatrics; University of California, San Francisco (UCSF) - Cardiovascular Research Institute

Mats Ljungman

University of Michigan at Ann Arbor - Department of Radiation Oncology; University of Michigan at Ann Arbor - Department of Environmental Health Sciences; University of Michigan at Ann Arbor - Center for RNA Biomedicine

Peter Fraser

Florida State University - Department of Biological Science; The Babraham Institute - Nuclear Dynamics Program; Florida State University - Center for Genomics and Personalized Medicine

Ferhat Ay

La Jolla Institute for Allergy and Immunology (LIAI); University of California, San Diego (UCSD) - School of Medicine

David M. Gilbert

Florida State University - Department of Biological Science; Florida State University - Center for Genomics and Personalized Medicine

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Abstract

The temporal order of DNA replication (replication timing, RT) is highly coupled with genome architecture, but cis-elements regulating spatio-temporal control of replicatio 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.

Suggested Citation

Sima, Jiao and Chakraborty, Abhijit and Dileep, Vishnu and Michalski, Marco and Rivera-Mulia, Juan Carlos and Trevilla-Garcia, Claudia and Klein, Kyle N. and Bartlett, Daniel and Washburn, Brian K. and Paulsen, Michelle T. and Vera, Daniel and Nora, Elphège P. and Kraft, Katerina and Mundlos, Stefan and Bruneau, Benoit G. and Ljungman, Mats and Fraser, Peter and Ay, Ferhat and Gilbert, David M., Identification of cis Elements for Spatio-temporal Control of DNA Replication (2018). Available at SSRN: https://ssrn.com/abstract=3188454 or http://dx.doi.org/10.2139/ssrn.3188454
This version of the paper has not been formally peer reviewed.

Jiao Sima

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Abhijit Chakraborty

La Jolla Institute for Allergy and Immunology (LIAI)

9420 Athena Cir
La Jolla, CA 92037
United States

Vishnu Dileep

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Marco Michalski

The Babraham Institute - Nuclear Dynamics Program

Babraham Research Campus
Babraham, Cambridge, England CB22 3AT
United Kingdom

Juan Carlos Rivera-Mulia

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Claudia Trevilla-Garcia

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Kyle N. Klein

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Daniel Bartlett

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Brian K. Washburn

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Michelle T. Paulsen

University of Michigan at Ann Arbor - Department of Pathology

Ann Arbor, MI 48109,
United States

University of Michigan at Ann Arbor - Department of Environmental Health Sciences

1415 Washington Heights
Ann Arbor, MI 48109-2800
United States

University of Michigan at Ann Arbor - Center for RNA Biomedicine

1150 W. Medical Center Dr.
Ann Arbor, MI 48109-0600
United States

Daniel Vera

Florida State University - Center for Genomics and Personalized Medicine

Tallahassee, FL 32306-4295
United States

Elphège P. Nora

University of California, San Francisco (UCSF) - Gladstone Institute of Cardiovascular Disease

1650 OWENS STREET
San Francisco, CA 94158
United States

University of California, San Francisco (UCSF) - Roddenberry Center for Stem Cell Biology and Medicine

1650 OWENS STREET
San Francisco, CA 94158
United States

University of California, San Francisco (UCSF) - Department of Pediatrics

550 16th Street, Box 0110
San Francisco, CA 94143
United States

University of California, San Francisco (UCSF) - Cardiovascular Research Institute

555 Mission Bay Boulevard South
San Francisco, CA 94158
United States

Katerina Kraft

Max Planck Society for the Advancement of the Sciences - Rearch Group Development & Disease

Ihnestraße 63-73
Berlin, 14195
Germany

Charité - Universitätsmedizin Berlin - Institute for Medical and Human Genetics

Berlin, 13353
Germany

Stefan Mundlos

Max Planck Society for the Advancement of the Sciences - Rearch Group Development & Disease

Ihnestraße 63-73
Berlin, 14195
Germany

Charité - Universitätsmedizin Berlin - Institute for Medical and Human Genetics

Berlin, 13353
Germany

Benoit G. Bruneau

University of California, San Francisco (UCSF) - Gladstone Institute of Cardiovascular Disease

1650 OWENS STREET
San Francisco, CA 94158
United States

University of California, San Francisco (UCSF) - Roddenberry Center for Stem Cell Biology and Medicine

1650 OWENS STREET
San Francisco, CA 94158
United States

University of California, San Francisco (UCSF) - Department of Pediatrics

550 16th Street, Box 0110
San Francisco, CA 94143
United States

University of California, San Francisco (UCSF) - Cardiovascular Research Institute

555 Mission Bay Boulevard South
San Francisco, CA 94158
United States

Mats Ljungman

University of Michigan at Ann Arbor - Department of Radiation Oncology

1500 E Medical Center Dr.
UH B2C490
Ann Arbor, MI 48109-5010
United States

University of Michigan at Ann Arbor - Department of Environmental Health Sciences

1415 Washington Heights
Ann Arbor, MI 48109-2800
United States

University of Michigan at Ann Arbor - Center for RNA Biomedicine

1150 W. Medical Center Dr.
Ann Arbor, MI 48109-0600
United States

Peter Fraser

Florida State University - Department of Biological Science

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

The Babraham Institute - Nuclear Dynamics Program

Babraham Research Campus
Babraham, Cambridge, England CB22 3AT
United Kingdom

Florida State University - Center for Genomics and Personalized Medicine

Tallahassee, FL 32306-4295
United States

Ferhat Ay

La Jolla Institute for Allergy and Immunology (LIAI)

9420 Athena Cir
La Jolla, CA 92037
United States

University of California, San Diego (UCSD) - School of Medicine

9500 Gilman Drive
MC 0507
La Jolla, CA 92093
United States

David M. Gilbert (Contact Author)

Florida State University - Department of Biological Science ( email )

319 Stadium Drive
Tallahassee, FL 32306-4295
United States

Florida State University - Center for Genomics and Personalized Medicine ( email )

Tallahassee, FL 32306-4295
United States