NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE114619 Query DataSets for GSE114619
Status Public on Jan 21, 2019
Title Identification of cis elements for temporal and spatial control of DNA replication [Capture Hi-C]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary DNA replication occurs in units of chromatin higher order organization (Topologically Associating Domains, or TADs; replication domains, or RDs), which self-organize in 3D into sub-nuclear compartments of early or late replicating chromatin. However, identification of cis-elements regulating replication timing (RT) and sub-nuclear compartments has been a major challenge in the field. Through an extensive series of CRISPR mediated deletion and inversions at a pluripotency associated domain (DppA2/4) in mouse embryonic stem cells (mESCs), we have identified cis-regulatory “early replication control elements” (ERCEs) that mediate early replication and A/B compartmentalization. We show that CTCF/cohesin loops, including the TAD boundaries, were dispensable, and multiple internal DNA segments were necessary for the domain’s early replication in a partially redundant fashion. These segments were also sufficient to maintain early replication in the context of large inversions, irrespective of TAD boundaries. High-resolution capture Hi-C of this region revealed three sites of major contact that also displayed prominent chromatin features. Targeted deletion of all three contact points, which do not include the major mapped replication origins, caused a complete shift to late replication and association with compartment B, equivalent to the switch during lineage commitment. Individual and pair-wise deletions confirmed their partial redundancy and interdependency in giving rise to domain-wise RT patterns, and suggest the importance of long-range interactions. ERCEs are enriched in properties of strong or super-enhancers, and regulate gene expression, although transcription itself is not sufficient in driving early replication. In sum, our results have revealed the first cis-elements regulating the temporal and spatial control of DNA replication that is independent of transcription.
 
Overall design Capture Hi-C profiles in mESCs with a bait in DppA2/4 domain.
 
Contributor(s) Sima J
Citation(s) 30595451
Submission date May 17, 2018
Last update date Jan 27, 2019
Contact name David M Gilbert
Organization name Florida State University
Department Biology
Lab Gilbert
Street address 319 Stadium Drive
City Tallahassee
State/province FL
ZIP/Postal code 32306-4295
Country USA
 
Platforms (1)
GPL21626 NextSeq 550 (Mus musculus)
Samples (14)
GSM3145928 mESC [Capture Hi-C]
GSM3145929 NPC [Capture Hi-C]
GSM3579858 100k.del.C3 [Capture Hi-C]
This SubSeries is part of SuperSeries:
GSE114139 Identification of cis elements for temporal and spatial control of DNA replication
Relations
BioProject PRJNA471924
SRA SRP148311

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE114619_RAW.tar 24.1 Mb (http)(custom) TAR (of MAT)
GSE114619_mESCAuxin2Days_RepCombined_10Kb.iced.mat.gz 709.9 Kb (ftp)(http) MAT
GSE114619_mESCUntreated_All_RepCombined_10Kb.iced.mat.gz 670.2 Kb (ftp)(http) MAT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap