sefOri: selecting the best-engineered sequence features to predict DNA replication origins

AbstractMotivationCell divisions start from replicating the double-stranded DNA, and the DNA replication process needs to be precisely regulated both spatially and temporally. The DNA is replicated starting from the DNA replication origins. A few successful prediction models were generated based on the assumption that the DNA replication origin regions have sequence level features like physicochemical properties significantly different from the other DNA regions.ResultsThis study proposed a feature selection procedure to further refine the classification model of the DNA replication origins. The experimental data demonstrated that as large as 26% improvement in the prediction accuracy may be achieved on the yeast Saccharomyces cerevisiae. Moreover, the prediction accuracies of the DNA replication origins were improved for all the four yeast genomes investigated in this study.Availability and implementationThe software sefOri version 1.0 was available at http://www.healthinformaticslab.org/supp/resources.php. An online server was also provided for the convenience of the users, and its web link may be found in the above-mentioned web page.Supplementary informationSupplementary data are available at Bioinformatics online.

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Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity in Drosophila

10.1101/539270 ◽

2019 ◽

Author(s):

Michelle Pherson, ◽

Ziva Misulovin ◽

Maria Gause ◽

Dale Dorsett

Keyword(s):

Dna Replication ◽

Sister Chromatid ◽

Sister Chromatid Cohesion ◽

Gene Promoters ◽

Replication Origins ◽

Genome Wide ◽

Chromatid Cohesion ◽

Dna Replication Origin ◽

Dna Replication Origins

AbstractCohesin consists of the Smc1-Smc3-Rad21 tripartite ring and the SA protein that interacts with Rad21. The Nipped-B protein loads cohesin topologically around chromosomes to mediate sister chromatid cohesion and facilitate long-range control of gene transcription. It is largely unknown how Nipped-B and cohesin associate specifically with gene promoters and transcriptional enhancers, or how sister chromatid cohesion is established. Here we use genome-wide chromatin immunoprecipitation in Drosophila cells to show that SA and the Fs(1)h (BRD4) BET domain protein help recruit Nipped-B and cohesin to enhancers and DNA replication origins, while the MED30 subunit of the Mediator complex directs Nipped-B and Rad21 to promoters. All enhancers and their neighboring promoters are close to DNA replication origins and bind SA with proportional levels of cohesin subunits. Most promoters are far from origins and lack SA, but bind Nipped-B and Rad21 with sub-proportional amounts of Smc1, indicating that they bind SA-deficient cohesin part of the time. Genetic data confirm that Nipped-B and Rad21 function together with Fs(1)h in vivo to facilitate Drosophila development. These findings demonstrate that Nipped-B and cohesin are differentially targeted to enhancers and promoters and suggest models for how SA and DNA replication help establish sister chromatid cohesion and facilitate enhancer-promoter communication. They indicate that SA is not an obligatory cohesin subunit but a factor that controls cohesin location on chromosomes.

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Ferritinophagy and Cell Cycle Control

Blood ◽

10.1182/blood.v128.22.sci-20.sci-20 ◽

2016 ◽

Vol 128 (22) ◽

pp. SCI-20-SCI-20 ◽

Cited By ~ 1

Author(s):

Francesca Carlomagno

Keyword(s):

Cell Cycle ◽

Dna Replication ◽

Replication Origin ◽

Phase Cell ◽

Cell Fractionation ◽

Replication Origins ◽

Cellular Iron ◽

Origin Activation ◽

Dna Replication Origin ◽

Dna Replication Origins

Abstract The autophagic degradation of the iron-storage macromolecule ferritin, called ferritinophagy, is critical to restore the appropriate cellular iron levels and influences systemic iron homeostasis. Under low iron conditions, nuclear receptor coactivator 4 (NCOA4) protein accumulates and promotes, as cargo receptor, ferritinophagy. We have recently demonstrated that mice carrying genetic ablation of NCOA4 were unable to mobilize iron from deposits, featuring tissue iron overload as well as mild anemia. Because of impaired ferritinophagy, NCOA4 null mice displayed a severe microcytic hypochromic anemia and ineffective erythropoiesis when fed with an iron low diet. Conversely, they poorly tolerated an iron rich diet, dying prematurely from iron toxicity. Since in previous studies we discovered that nuclear NCOA4 is a chromatin binding protein that acts as a negative regulator of DNA replication origin activation, inhibiting the MCM2-7 DNA helicase, we also investigated whether NCOA4 could regulate DNA replication as a function of iron bioavailability. Treatment with iron chelators promoted a G1 phase cell cycle arrest, blocking DNA replication origins activation. In cell fractionation experiments, we observed that iron depletion induced not only cytosolic but also nuclear NCOA4 stabilization, and by chromatin immunoprecipitation (CHIP) and co-immunoprecipitation assays, we demonstrated that NCOA4 enriches at canonical DNA replication origins increasing the binding to MCM2-7 complex. Silencing of NCOA4 induced an unscheduled activation of DNA replication under iron-depleted conditions that promotes replication stress and impairs cell viability. In conclusion, our data indicate NCOA4 as a novel key iron responsive protein able to couple DNA replication origin activation to cellular iron levels. Disclosures No relevant conflicts of interest to declare.

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In Xenopus Egg Extracts, DNA Replication Initiates Preferentially at or near Asymmetric AT Sequences

Molecular and Cellular Biology ◽

10.1128/mcb.00181-08 ◽

2008 ◽

Vol 28 (17) ◽

pp. 5265-5274 ◽

Cited By ~ 23

Author(s):

Slavica Stanojcic ◽

Jean-Marc Lemaitre ◽

Konstantin Brodolin ◽

Etienne Danis ◽

Marcel Mechali

Keyword(s):

Dna Replication ◽

Basal Layer ◽

Sperm Chromatin ◽

Sequence Specificity ◽

Replication Origins ◽

Egg Extracts ◽

Dna Replication Origin ◽

Dna Replication Origins ◽

Xenopus Egg Extracts ◽

Selection Of

ABSTRACT Previous observations led to the conclusion that in Xenopus eggs and during early development, DNA replication initiates at regular intervals but with no apparent sequence specificity. Conversely, here, we present evidence for site-specific DNA replication origins in Xenopus egg extracts. Using λ DNA, we show that DNA replication origins are activated in clusters in regions that contain closely spaced adenine or thymine asymmetric tracks used as preferential initiation sites. In agreement with these data, AT-rich asymmetric sequences added as competitors preferentially recruit origin recognition complexes and inhibit sperm chromatin replication by increasing interorigin spacing. We also show that the assembly of a transcription complex favors origin activity at the corresponding site without necessarily eliminating the other origins. Thus, although Xenopus eggs have the ability to replicate any kind of DNA, AT-rich domains or transcription factors favor the selection of DNA replication origins without increasing the overall efficiency of DNA synthesis. These results suggest that asymmetric AT-rich regions might be default elements that favor the selection of a DNA replication origin in a transcriptionally silent complex, whereas other epigenetic elements linked to the organization of domains for transcription may have further evolved over this basal layer of regulation.

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