scholarly journals Efficient, quick and easy-to-use DNA replication timing analysis with START-R suite

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Djihad Hadjadj ◽  
Thomas Denecker ◽  
Eva Guérin ◽  
Su-Jung Kim ◽  
Fabien Fauchereau ◽  
...  
Keyword(s):  
Dna Replication ◽  
Cell Fate ◽  
Web Application ◽  
Timing Analysis ◽  
Mutant Cell ◽  
Replication Timing ◽  
Experimental Conditions ◽  
Replication Process ◽  
Time Required ◽  
Dna Replication Timing

Abstract DNA replication must be faithful and follow a well-defined spatiotemporal program closely linked to transcriptional activity, epigenomic marks, intranuclear structures, mutation rate and cell fate determination. Among the readouts of the spatiotemporal program of DNA replication, replication timing analyses require not only complex and time-consuming experimental procedures, but also skills in bioinformatics. We developed a dedicated Shiny interactive web application, the START-R (Simple Tool for the Analysis of the Replication Timing based on R) suite, which analyzes DNA replication timing in a given organism with high-throughput data. It reduces the time required for generating and analyzing simultaneously data from several samples. It automatically detects different types of timing regions and identifies significant differences between two experimental conditions in ∼15 min. In conclusion, START-R suite allows quick, efficient and easier analyses of DNA replication timing for all organisms. This novel approach can be used by every biologist. It is now simpler to use this method in order to understand, for example, whether ‘a favorite gene or protein’ has an impact on replication process or, indirectly, on genomic organization (as Hi-C experiments), by comparing the replication timing profiles between wild-type and mutant cell lines.

scholarly journals New, easy, quick and efficient DNA replication timing analysis by high-throughput approaches

2019 ◽  
Author(s):  
Djihad Hadjadj ◽  
Thomas Denecker ◽  
Eva Guérin ◽  
Su-Jung Kim ◽  
Fabien Fauchereau ◽  
...  
Keyword(s):  
Dna Replication ◽  
Cell Fate ◽  
Web Application ◽  
Global Analysis ◽  
Timing Analysis ◽  
Replication Timing ◽  
Experimental Conditions ◽  
Spatio Temporal ◽  
Dna Replication Timing ◽  
Temporal Program

AbstractDNA replication must be faithful and follow a well-defined spatio-temporal program closely linked to transcriptional activity, epigenomic marks, intra-nuclear structures, mutation rate and cell fate determination. Among the readouts of the DNA replication spatio-temporal program, replication timing (RT) analyses require complex, precise and time-consuming experimental procedures, and the study of large-size computer files. We improved the RT protocol to speed it up and increase its quality and reproducibility. Also, we partly automated the RT protocol and developed a user-friendly software: the START-R suite (Simple Tool for the Analysis of the Replication Timing based on R). START-R suite is an open source web application using an R script and an HTML interface to analyze DNA replication timing in a given cell line with microarray or deep-sequencing results. This novel approach can be used by every biologist without requiring specific knowledge in bioinformatics. It also reduces the time required for generating and analyzing simultaneously data from several samples. START-R suite detects constant timing regions (CTR) but also, and this is a novelty, it identifies temporal transition regions (TTR) and detects significant differences between two experimental conditions. The informatic global analysis requires less than 10 minutes.

scholarly journals The Genetic Architecture of DNA Replication Timing in Human Pluripotent Stem Cells

2020 ◽  
Author(s):  
Qiliang Ding ◽  
Matthew M. Edwards ◽  
Michelle L. Hulke ◽  
Alexa N. Bracci ◽  
Ya Hu ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Sequences ◽  
Timing Analysis ◽  
Replication Timing ◽  
Histone Code ◽  
Replication Initiation ◽  
Histone Hyperacetylation ◽  
Stem Cell Lines ◽  
Early Replication ◽  
Dna Replication Timing

AbstractDNA replication follows a strict spatiotemporal program that intersects with chromatin structure and gene regulation. However, the genetic basis of the mammalian DNA replication timing program is poorly understood1–3. To systematically identify genetic regulators of DNA replication timing, we exploited inter-individual variation in 457 human pluripotent stem cell lines from 349 individuals. We show that the human genome’s replication program is broadly encoded in DNA and identify 1,617 cis-acting replication timing quantitative trait loci (rtQTLs4) – base-pair-resolution sequence determinants of replication initiation. rtQTLs function individually, or in combinations of proximal and distal regulators, to affect replication timing. Analysis of rtQTL locations reveals a histone code for replication initiation, composed of bivalent histone H3 trimethylation marks on a background of histone hyperacetylation. The H3 trimethylation marks are individually repressive yet synergize to promote early replication. We further identify novel positive and negative regulators of DNA replication timing, the former comprised of pluripotency-related transcription factors while the latter involve boundary elements. Human replication timing is controlled by a multi-layered mechanism that operates on target DNA sequences, is composed of dozens of effectors working combinatorially, and follows principles analogous to transcription regulation: a histone code, activators and repressors, and a promoter-enhancer logic.

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

2021 ◽  
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

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

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.

scholarly journals Rif1 Controls DNA Replication Timing in Yeast through the PP1 Phosphatase Glc7

Cell Reports ◽  
2014 ◽  
Vol 7 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Stefano Mattarocci ◽  
Maksym Shyian ◽  
Laure Lemmens ◽  
Pascal Damay ◽  
Dogus Murat Altintas ◽  
...  
Keyword(s):  
Dna Replication ◽  
Replication Timing ◽  
Dna Replication Timing

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
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