NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE159663 Query DataSets for GSE159663
Status Public on Sep 21, 2021
Title DNA methylation maintains integrity of higher order genome architecture (Nanopore)
Organism Homo sapiens
Experiment type Genome variation profiling by high throughput sequencing
Summary DNA replication timing and 3D chromatin organisation are associated with epigenomic changes across large domains during human differentiation and cancer progression. However, it is unclear if epigenome changes, in particular cancer-associated DNA hypomethylation, is a consequence or cause of changes observed in higher order genome architecture. Here, we compare replication timing profiles and three dimensional (3D) genome organisation, using Hi-C and single cell Repli-Seq in the DNMT1 and DNMT3B DNA methyltransferases double knockout hypomethylated DKO1 colorectal cancer cell line and its parental HCT116 cell line. We find that the hypomethylated cells show a profound loss of replication timing precision, gain of single cell replication timing heterogeneity and loss of chromatin conformation integrity. Discrete regions, that undergo a large change in replication timing in the hypomethylated cells, are associated with a loss of allelic replication timing and shrinking of late replicating Partially Methylated Domain (PMD) boundaries. In contrast, conservation of replication timing after DNA methylation depletion at PMDs is associated with the formation of new H3K9me3/H3K4me3 bivalent domains which may serve to prevent ectopic transcription and maintain cell viability. Together our results show that a loss of global methylation, a common hallmark of cancer, directly impacts on the precision of replication timing and contribute to deregulation of the 3D chromatin architecture.
 
Overall design Repli-Seq, single cell Repli-Seq, Hi-C, WGBS and Nanopore sequencing was conducted in HCT116 human colorectal cancer cell line and the same cell line with knockout of DNMT1 and DNMT3B (DKO1) (Rhee et al. 2002).
 
Contributor(s) Du Q, Clark SJ
Citation(s) 34551299
Submission date Oct 20, 2020
Last update date Dec 26, 2021
Contact name Qian Du
E-mail(s) [email protected]
Organization name Garvan Institute of Medical Research
Street address 384 Victoria St
City Darlinghurst
State/province NSW
ZIP/Postal code 2010
Country Australia
 
Platforms (1)
GPL26167 PromethION (Homo sapiens)
Samples (2)
GSM4837257 HCT116 WT Nanopore-Seq
GSM4837258 HCT116 DKO1 Nanopore-Seq
This SubSeries is part of SuperSeries:
GSE158011 DNA methylation maintains integrity of higher order genome architecture
Relations
BioProject PRJNA670129
SRA SRP287795

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
GSE159663_RAW.tar 951.9 Mb (http)(custom) TAR (of VCF)
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