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

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.

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

The Plant Cell ◽

10.1105/tpc.17.00037 ◽

2017 ◽

Vol 29 (9) ◽

pp. 2126-2149 ◽

Cited By ~ 11

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

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

Genes ◽

10.3390/genes10030196 ◽

2019 ◽

Vol 10 (3) ◽

pp. 196 ◽

Cited By ~ 6

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.

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

PLoS ONE ◽

10.1371/journal.pone.0000722 ◽

2007 ◽

Vol 2 (8) ◽

pp. e722 ◽

Cited By ~ 13

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

10.1101/542902 ◽

2019 ◽

Cited By ~ 2

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

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Faculty Opinions recommendation of Conserved forkhead dimerization motif controls DNA replication timing and spatial organization of chromosomes in S. cerevisiae.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727380810.793535287 ◽

2017 ◽

Author(s):

Catherine Fox

Keyword(s):

Dna Replication ◽

Spatial Organization ◽

Replication Timing ◽

Dna Replication Timing

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Faculty Opinions recommendation of Stability of patient-specific features of altered DNA replication timing in xenografts of primary human acute lymphoblastic leukemia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727545410.793549651 ◽

2018 ◽

Author(s):

Domenico Maiorano

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Dna Replication ◽

Lymphoblastic Leukemia ◽

Replication Timing ◽

Patient Specific ◽

Dna Replication Timing ◽

Human Acute Lymphoblastic Leukemia

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TIGER: inferring DNA replication timing from whole-genome sequence data

Bioinformatics ◽

10.1093/bioinformatics/btab166 ◽

2021 ◽

Cited By ~ 1

Author(s):

Amnon Koren ◽

Dashiell J Massey ◽

Alexa N Bracci

Keyword(s):

Dna Replication ◽

Genome Sequence ◽

Genomic Dna ◽

Sequence Data ◽

Replication Timing ◽

Whole Genome Sequence ◽

Supplementary Information ◽

Whole Genome ◽

Genome Sequence Data ◽

Dna Replication Timing

Abstract Motivation Genomic DNA replicates according to a reproducible spatiotemporal program, with some loci replicating early in S phase while others replicate late. Despite being a central cellular process, DNA replication timing studies have been limited in scale due to technical challenges. Results We present TIGER (Timing Inferred from Genome Replication), a computational approach for extracting DNA replication timing information from whole genome sequence data obtained from proliferating cell samples. The presence of replicating cells in a biological specimen leads to non-uniform representation of genomic DNA that depends on the timing of replication of different genomic loci. Replication dynamics can hence be observed in genome sequence data by analyzing DNA copy number along chromosomes while accounting for other sources of sequence coverage variation. TIGER is applicable to any species with a contiguous genome assembly and rivals the quality of experimental measurements of DNA replication timing. It provides a straightforward approach for measuring replication timing and can readily be applied at scale. Availability and Implementation TIGER is available at https://github.com/TheKorenLab/TIGER. Supplementary information Supplementary data are available at Bioinformatics online

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Asymmetrical deposition and modification of histone H3 variants are essential for zygote development

Life Science Alliance ◽

10.26508/lsa.202101102 ◽

2021 ◽

Vol 4 (8) ◽

pp. e202101102

Author(s):

Machika Kawamura ◽

Satoshi Funaya ◽

Kenta Sugie ◽

Masataka G Suzuki ◽

Fugaku Aoki

Keyword(s):

Dna Replication ◽

Mrna Expression ◽

Detrimental Effect ◽

Histone H3 ◽

Replication Timing ◽

Male And Female ◽

Zygote Development ◽

The One ◽

Dna Replication Timing ◽

Incorporation Efficiency

The pericentromeric heterochromatin of one-cell embryos forms a unique, ring-like structure around the nucleolar precursor body, which is absent in somatic cells. Here, we found that the histone H3 variants H3.1 and/or H3.2 (H3.1/H3.2) were localized asymmetrically between the male and female perinucleolar regions of the one-cell embryos; moreover, asymmetrical histone localization influenced DNA replication timing. The nuclear deposition of H3.1/3.2 in one-cell embryos was low relative to other preimplantation stages because of reduced H3.1/3.2 mRNA expression and incorporation efficiency. The forced incorporation of H3.1/3.2 into the pronuclei of one-cell embryos triggered a delay in DNA replication, leading to developmental failure. Methylation of lysine residue 27 (H3K27me3) of the deposited H3.1/3.2 in the paternal perinucleolar region caused this delay in DNA replication. These results suggest that reduced H3.1/3.2 in the paternal perinucleolar region is essential for controlled DNA replication and preimplantation development. The nuclear deposition of H3.1/3.2 is presumably maintained at a low level to avoid the detrimental effect of K27me3 methylation on DNA replication in the paternal perinucleolar region.

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High-throughput analysis of DNA replication in single human cells reveals constrained variability in the location and timing of replication initiation

10.1101/2021.05.14.443897 ◽

2021 ◽

Author(s):

Dashiell J Massey ◽

Amnon Koren

Keyword(s):

Dna Replication ◽

Replication Origin ◽

Replication Timing ◽

S Phase ◽

Human Cells ◽

Replication Initiation ◽

High Throughput Analysis ◽

Timing Variability ◽

Fixed Set ◽

Fixed Order

DNA replication occurs throughout the S phase of the cell cycle, initiating from replication origin loci that fire at different times. Debate remains about whether origins are a fixed set of loci used across all cells or a loose agglomeration of potential origins used stochastically in individual cells, and about how consistent their firing time during S phase is across cells. Here, we develop an approach for profiling DNA replication in single human cells and apply it to 2,305 replicating cells spanning the entire S phase. The resolution and scale of the data enabled us to specifically analyze initiation sites and show that these sites have confined locations that are consistently used among individual cells. Further, we find that initiation sites are activated in a similar, albeit not fixed, order across cells. Taken together, our results suggest that replication timing variability is constrained both spatially and temporally, and that the degree of variation is consistent across human cell lines.

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