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UNIVERSITY OF SOUTHERN CALIFORNIA

M O L E C U L A R & C O M P U TAT I O NA L B I O LO G Y
COLLOQUIUM SERIES

David Gilbert, PhD


J. Herbert Taylor Distinguished Professor of
Molecular Biology
from
Florida State University
Department of Biological Science
will present on

"Regulation of Replication Timing


and Chromosome Architecture”

Abstract: The temporal order of DNA replication (replication


timing [RT]) is highly coupled with genome architecture, but cis-
elements regulating either remain elusive. We created a series of
CRISPR-mediated deletions and inversions of a pluripotency-
associated topologically associating domain (TAD) in mouse ESCs.
Friday, February 22, 2019 CTCF-associated domain boundaries were dispensable for RT.
12:00 pm to 1:00 pm
CTCF protein depletion weakened most TAD boundaries but had
no effect on RT or A/B compartmentalization genome-wide. By
Ray R. Irani Hall
1050 Childs Way, RRI 101 contrast, deletion of three intra-TAD CTCF-independent 3D
Los Angeles, CA 90089-2910 contact sites caused a domain-wide earlyto- late RT shift, an A-to-
B compartment switch, weakening of TAD architecture, and loss
of transcription. The dispensability of TAD boundaries and the
For additional information,
necessity of these ‘‘early replication control elements’’ (ERCEs)
contact:
was validated by deletions and inversions at additional domains.
Oscar Aparicio, PhD
Our results demonstrate that discrete cis-regulatory elements
oaparici@usc.edu
orchestrate domain-wide RT, A/B compartmentalization, TAD
Jen Nelson architecture, and transcription, revealing fundamental principles
jmbrewer@usc.edu linking genome structure and function.