scholarly journals Cohesin-mediated genome architecture does not define DNA replication timing domains

2019 ◽  
Author(s):  
Phoebe Oldach ◽  
Conrad A Nieduszynski
Keyword(s):  
Dna Replication ◽  
Genome Organization ◽  
Mammalian Cells ◽  
Replication Timing ◽  
S Phase ◽  
Genome Architecture ◽  
3D Genome ◽  
Synchronized Cells ◽  
Dna Replication Timing ◽  
Phase Entry

3D genome organization is strongly predictive of DNA replication timing in mammalian cells. This work tested the extent to which loop-based genome architecture acts as a regulatory unit of replication timing by using an auxin-inducible system for acute cohesin ablation. Cohesin ablation in a population of cells in asynchronous culture was shown not to disrupt patterns of replication timing as assayed by replication sequencing (RepliSeq) or BrdU-focus microscopy. Furthermore, cohesin ablation prior to S phase entry in synchronized cells was similarly shown to not impact replication timing patterns. These results suggest that cohesin-mediated genome architecture is not required for the execution of replication timing patterns in S phase, nor for the establishment of replication timing domains in G1.

scholarly journals Cohesin-Mediated Genome Architecture Does Not Define DNA Replication Timing Domains

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 196 ◽  
Author(s):  
Phoebe Oldach ◽  
Conrad A. Nieduszynski
Keyword(s):  
Dna Replication ◽  
Genome Organization ◽  
Mammalian Cells ◽  
Replication Timing ◽  
S Phase ◽  
Genome Architecture ◽  
3D Genome ◽  
Synchronized Cells ◽  
Dna Replication Timing ◽  
Phase Entry

3D genome organization is strongly predictive of DNA replication timing in mammalian cells. This work tested the extent to which loop-based genome architecture acts as a regulatory unit of replication timing by using an auxin-inducible system for acute cohesin ablation. Cohesin ablation in a population of cells in asynchronous culture was shown not to disrupt patterns of replication timing as assayed by replication sequencing (RepliSeq) or BrdU-focus microscopy. Furthermore, cohesin ablation prior to S phase entry in synchronized cells was similarly shown to not impact replication timing patterns. These results suggest that cohesin-mediated genome architecture is not required for the execution of replication timing patterns in S phase, nor for the establishment of replication timing domains in G1.

scholarly journals DNA methylation is required to maintain DNA replication timing precision and 3D genome integrity

2020 ◽  
Author(s):  
Qian Du ◽  
Grady C. Smith ◽  
Phuc Loi Luu ◽  
James M. Ferguson ◽  
Nicola J. Armstrong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Replication ◽  
Replication Timing ◽  
Genome Architecture ◽  
Genome Organisation ◽  
Dna Hypomethylation ◽  
3D Genome ◽  
Timing Precision ◽  
The Impact ◽  
Dna Replication Timing

AbstractDNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer higher order genome architecture. Here, we use Hi-C and single cell Repli-Seq, in the colorectal cancer DNMT1 and DNMT3B DNA methyltransferases double knockout model, to determine the impact of DNA hypomethylation on replication timing and 3D genome organisation. First, we find that the hypomethylated cells show a striking loss of replication timing precision with gain of cell-to-cell replication timing heterogeneity and loss of 3D genome compartmentalisation. Second, hypomethylated regions that undergo a large change in replication timing also show loss of allelic replication timing, including at cancer-related genes. Finally, we observe the formation of broad ectopic H3K4me3-H3K9me3 domains across hypomethylated regions where late replication is maintained, that potentially prevent aberrant transcription and loss of genome organisation after DNA demethylation. Together, our results highlight a previously underappreciated role for DNA methylation in maintenance of 3D genome architecture.

scholarly journals DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity

Cell Reports ◽  
2021 ◽  
Vol 36 (12) ◽  
pp. 109722
Author(s):  
Qian Du ◽  
Grady C. Smith ◽  
Phuc Loi Luu ◽  
James M. Ferguson ◽  
Nicola J. Armstrong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Replication ◽  
Genome Organization ◽  
Replication Timing ◽  
3D Genome ◽  
Timing Precision ◽  
Dna Replication Timing

scholarly journals DNA Replication Timing Enters the Single-Cell Era

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 221 ◽  
Author(s):  
Ichiro Hiratani ◽  
Saori Takahashi
Keyword(s):  
Dna Replication ◽  
Single Cell ◽  
Cell Population ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Replication Timing ◽  
3D Genome ◽  
Population Analyses ◽  
Dna Replication Timing

In mammalian cells, DNA replication timing is controlled at the level of megabase (Mb)-sized chromosomal domains and correlates well with transcription, chromatin structure, and three-dimensional (3D) genome organization. Because of these properties, DNA replication timing is an excellent entry point to explore genome regulation at various levels and a variety of studies have been carried out over the years. However, DNA replication timing studies traditionally required at least tens of thousands of cells, and it was unclear whether the replication domains detected by cell population analyses were preserved at the single-cell level. Recently, single-cell DNA replication profiling methods became available, which revealed that the Mb-sized replication domains detected by cell population analyses were actually well preserved in individual cells. In this article, we provide a brief overview of our current knowledge on DNA replication timing regulation in mammals based on cell population studies, outline the findings from single-cell DNA replication profiling, and discuss future directions and challenges.

scholarly journals Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips

2017 ◽  
Vol 29 (9) ◽  
pp. 2126-2149 ◽  
Author(s):  
Emily E. Wear ◽  
Jawon Song ◽  
Gregory J. Zynda ◽  
Chantal LeBlanc ◽  
Tae-Jin Lee ◽  
...  
Keyword(s):  
Zea Mays ◽  
Dna Replication ◽  
Genomic Analysis ◽  
Replication Timing ◽  
S Phase ◽  
Root Tips ◽  
Dna Replication Timing

Control of DNA replication timing in the 3D genome

2019 ◽  
Vol 20 (12) ◽  
pp. 721-737 ◽  
Author(s):  
Claire Marchal ◽  
Jiao Sima ◽  
David M. Gilbert
Keyword(s):  
Dna Replication ◽  
Replication Timing ◽  
3D Genome ◽  
Dna Replication Timing

scholarly journals Genome-wide stability of the DNA replication program in single mammalian cells

2017 ◽  
Author(s):  
Saori Takahashi ◽  
Hisashi Miura ◽  
Takahiro Shibata ◽  
Koji Nagao ◽  
Katsuzumi Okumura ◽  
...  
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Developmental Plasticity ◽  
Embryonic Stem ◽  
Replication Timing ◽  
Small Degree ◽  
3D Genome ◽  
Inactive X Chromosome ◽  
Genome Wide ◽  
Individual Mouse

ABSTRACTHere, we report the establishment of a single-cell DNA replication sequencing method, scRepli-seq, which is a simple genome-wide methodology that measures copy number differences between replicated and unreplicated DNA. Using scRepli-seq, we demonstrate that replication domain organization is conserved among individual mouse embryonic stem cells (mESCs). Differentiated mESCs exhibited distinct replication profiles, which were conserved from cell to cell. Haplotype-resolved scRepli-seq revealed similar replication timing profiles of homologous autosomes, while the inactive X chromosome was clearly replicated later than its active counterpart. However, a small degree of cell-to-cell replication timing heterogeneity was present, and we discovered that developmentally regulated domains are a source of such variability, suggesting a link between cell-to-cell heterogeneity and developmental plasticity. Together, our results form a foundation for single-cell-level understanding of DNA replication regulation and provide insights into 3D genome organization.

scholarly journals Precise switching of DNA replication timing in the GC content transition area in the human major histocompatibility complex.

1997 ◽  
Vol 17 (7) ◽  
pp. 4043-4050 ◽  
Author(s):  
T Tenzen ◽  
T Yamagata ◽  
T Fukagawa ◽  
K Sugaya ◽  
A Ando ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Dna Replication ◽  
Replication Timing ◽  
S Phase ◽  
Chromosome Band ◽  
Switch Region ◽  
Switch Point ◽  
Junction Area ◽  
Histocompatibility Complex ◽  
Dna Replication Timing

The human genome is composed of long-range G+C% (GC%) mosaic structures thought to be related to chromosome bands. We previously reported a boundary of megabase-sized GC% mosaic domains at the junction area between major histocompatibility complex (MHC) classes II and III, proposing it as a possible chromosome band boundary. DNA replication timing during the S phase is known to be correlated cytogenetically with chromosome band zones, and thus the band boundaries have been predicted to contain a switch point for DNA replication timing. In this study, to identify to the nucleotide sequence level the replication switch point during the S phase, we determined the precise DNA replication timing for MHC classes II and III, focusing on the junction area. To do this, we used PCR-based quantitation of nascent DNA obtained from synchronized human myeloid leukemia HL60 cells. The replication timing changed precisely in the boundary region with a 2-h difference between the two sides, supporting the prediction that this region may be a chromosome band boundary. We supposed that replication fork movement terminates (pauses) or significantly slows in the switch region, which contains dense Alu clusters; polypurine/polypyrimidine tracts; di-, tri-, or tetranucleotide repeats; and medium-reiteration-frequency sequences. Because the nascent DNA in the switch region was recovered at low efficiency, we investigated whether this region is associated with the nuclear scaffold and found three scaffold-associated regions in and around the switch region.

scholarly journals Global Profiling of DNA Replication Timing and Efficiency Reveals that Efficient Replication/Firing Occurs Late during S-Phase in S. pombe

PLoS ONE ◽  
2007 ◽  
Vol 2 (8) ◽  
pp. e722 ◽  
Author(s):  
Majid Eshaghi ◽  
R. Krishna M. Karuturi ◽  
Juntao Li ◽  
Zhaoqing Chu ◽  
Edison T. Liu ◽  
...  
Keyword(s):  
Dna Replication ◽  
Replication Timing ◽  
S Phase ◽  
Efficient Replication ◽  
Dna Replication Timing
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