Identification of cis Elements for Spatio-temporal Control of DNA Replication
2018
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
CRISPRmediated deletions and inversions and high-resolution capture Hi-C of a pluripotency associated domain (DppA2/4) in mouse embryonic stem cells. Whereas
CTCFmediated loops and
chromatindomain boundaries were dispensable, deletion of three intra-domain prominent
CTCF-independent 3D contact sites caused a domain-wide early to late switch in RT, shift in sub-nuclear
chromatincompartment and loss of transcriptional activity, These early replication control elements (ERCEs) display prominent
chromatinfeatures 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 elementsmediate domain-wide RT,
chromatincompartmentalization, and transcription, representing a major advance in dissecting the relationship between genome structure and function.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
92
References
1
Citations
NaN
KQI