scholarly journals Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

2019 ◽  
Author(s):  
Markus Lindberg ◽  
Martin Boström ◽  
Kerryn Elliott ◽  
Erik Larsson
Keyword(s):  
Uv Light ◽  
Promoter Regions ◽  
Additional Information ◽  
Uv Mutation ◽  
Pyrimidine Dimers ◽  
Genome Wide ◽  
Extended Sequence ◽  
Dna Photoproducts ◽  
Sequence Characteristics ◽  
Mutational Process

ABSTRACTMutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG>TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer patterns improves modeling of UV mutation rate, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.

scholarly journals Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

2019 ◽  
Vol 116 (41) ◽  
pp. 20411-20417 ◽  
Author(s):  
Markus Lindberg ◽  
Martin Boström ◽  
Kerryn Elliott ◽  
Erik Larsson
Keyword(s):  
Uv Light ◽  
Promoter Regions ◽  
Additional Information ◽  
Pyrimidine Dimers ◽  
Genome Wide ◽  
Extended Sequence ◽  
Dna Photoproducts ◽  
Sequence Characteristics ◽  
Mutational Processes ◽  
Mutational Process

Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here, we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG > TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer contextual patterns improves modeling of UV mutations, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.

scholarly journals The effect of flanking bases on direct and triplet sensitized cyclobutane pyrimidine dimer formation in DNA depends on the dipyrimidine, wavelength and the photosensitizer

2021 ◽  
Author(s):  
Chen Lu ◽  
Natalia Eugenia Gutierrez-Bayona ◽  
John-Stephen Taylor
Keyword(s):  
Uv Light ◽  
Pyrimidine Dimer ◽  
Flanking Sequence ◽  
Quenching Mechanism ◽  
Cyclobutane Pyrimidine Dimers ◽  
Sequence Dependence ◽  
Pyrimidine Dimers ◽  
Skin Cancers ◽  
A Charge ◽  
C To T Mutations

Abstract Cyclobutane pyrimidine dimers (CPDs) are the major products of DNA produced by direct absorption of UV light, and result in C to T mutations linked to human skin cancers. Most recently a new pathway to CPDs in melanocytes has been discovered that has been proposed to arise from a chemisensitized pathway involving a triplet sensitizer that increases mutagenesis by increasing the percentage of C-containing CPDs. To investigate how triplet sensitization may differ from direct UV irradiation, CPD formation was quantified in a 129-mer DNA designed to contain all 64 possible NYYN sequences. CPD formation with UVB light varied about 2-fold between dipyrimidines and 12-fold with flanking sequence and was most frequent at YYYR and least frequent for GYYN sites in accord with a charge transfer quenching mechanism. In contrast, photosensitized CPD formation greatly favored TT over C-containing sites, more so for norfloxacin (NFX) than acetone, in accord with their differing triplet energies. While the sequence dependence for photosensitized TT CPD formation was similar to UVB light, there were significant differences, especially between NFX and acetone that could be largely explained by the ability of NFX to intercalate into DNA.

scholarly journals Genome-Wide Identification and Expression Analyses of CONSTANS-Like Family Genes in Cucumber (Cucumis sativus L.)

2021 ◽  
Author(s):  
Zhen Tian ◽  
Xiaodong Qin ◽  
Hui Wang ◽  
Ji Li ◽  
Jinfeng Chen
Keyword(s):  
Floral Induction ◽  
Structural Characteristics ◽  
Expression Patterns ◽  
Evolutionary Relationship ◽  
Biological Functions ◽  
Promoter Regions ◽  
Cucumis Sativus L ◽  
Cis Acting ◽  
Genome Wide ◽  
Induction Process

AbstractThe CONSTANS-like (COL) gene family is one of the plant-specific transcription factor families that play important roles in plant growth and development. However, the knowledge of COLs related in cucumber is limited, and their biological functions, especially in the photoperiod-dependent flowering process, are still unclear. In this study, twelve CsaCOL genes were identified in the cucumber genome. Phylogenetic and conserved motif analyses provided insights into the evolutionary relationship between the CsaCOLs. Further, the comparative genome analysis revealed that COL genes are conserved in different plant species, especially collinearity gene pairs related to CsaCOL5. Ten kinds of cis-acting elements were vividly detected in CsaCOLs promoter regions, including five light-responsive elements, which echo the diurnal rhythm expression patterns of seven CsaCOL genes under SD and LD photoperiod regimes. Combined with the expression data of developmental stage, three CsaCOL genes are involved in the flowering network and play pivotal roles for the floral induction process. Our results provide useful information for further elucidating the structural characteristics, expression patterns, and biological functions of COL family genes in many plants

scholarly journals Genome-wide identification, evolution, and expression analysis of the NPR1-like gene family in pears

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12617
Author(s):  
Yarui Wei ◽  
Shuliang Zhao ◽  
Na Liu ◽  
Yuxing Zhang
Keyword(s):  
Gene Family ◽  
Stress Responses ◽  
Systemic Acquired Resistance ◽  
Acquired Resistance ◽  
Signal Transduction Pathway ◽  
Promoter Regions ◽  
Systematic Analysis ◽  
Genome Wide ◽  
Pathogenesis Related ◽  
Genome Level

The NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1) plays a master regulatory role in the salicylic acid (SA) signal transduction pathway and plant systemic acquired resistance (SAR). Members of the NPR1-like gene family have been reported to the associated with biotic/abiotic stress in many plants, however the genome-wide characterization of NPR1-like genes has not been carried out in Chinese pear (Pyrus bretschneideri Reld). In this study, a systematic analysis was conducted on the characteristics of the NPR1-like genes in P. bretschneideri Reld at the whole-genome level. A total nine NPR1-like genes were detected which eight genes were located on six chromosomes and one gene was mapped to scaffold. Based on the phylogenetic analysis, the nine PbrNPR1-like proteins were divided into three clades (Clades I–III) had similar gene structure, domain and conserved motifs. We sorted the cis-acting elements into three clades, including plant growth and development, stress responses, and hormone responses in the promoter regions of PbrNPR1-like genes. The result of qPCR analysis showed that expression diversity of PbrNPR1-like genes in various tissues. All the genes were up-regulated after SA treatment in leaves except for Pbrgene8896. PbrNPR1-like genes showed circadian rhythm and significantly different expression levels after inoculation with Alternaria alternata. These findings provide a solid insight for understanding the functions and evolution of PbrNPR1-like genes in Chinese pear.

scholarly journals High similarity among ChEC-seq datasets

2021 ◽  
Author(s):  
Chitvan Mittal ◽  
Matthew J. Rossi ◽  
B. Franklin Pugh
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Regulators ◽  
Micrococcal Nuclease ◽  
High Similarity ◽  
Dna Interactions ◽  
Promoter Regions ◽  
Genome Wide ◽  
A Genome ◽  
Protein Dna Interactions ◽  
Negative Controls

AbstractChEC-seq is a method used to identify protein-DNA interactions across a genome. It involves fusing micrococcal nuclease (MNase) to a protein of interest. In principle, specific genome-wide interactions of the fusion protein with chromatin result in local DNA cleavages that can be mapped by DNA sequencing. ChEC-seq has been used to draw conclusions about broad gene-specificities of certain protein-DNA interactions. In particular, the transcriptional regulators SAGA, TFIID, and Mediator are reported to generally occupy the promoter/UAS of genes transcribed by RNA polymerase II in yeast. Here we compare published yeast ChEC-seq data performed with a variety of protein fusions across essentially all genes, and find high similarities with negative controls. We conclude that ChEC-seq patterning for SAGA, TFIID, and Mediator differ little from background at most promoter regions, and thus cannot be used to draw conclusions about broad gene specificity of these factors.

scholarly journals Assessment of transcriptional importance of cell line-specific features based on GTRD and FANTOM5 data

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243332
Author(s):  
Ruslan N. Sharipov ◽  
Yury V. Kondrakhin ◽  
Anna S. Ryabova ◽  
Ivan S. Yevshin ◽  
Fedor A. Kolpakov
Keyword(s):  
Regression Analysis ◽  
Cell Line ◽  
Transcriptional Start Site ◽  
Regulation Of Transcription ◽  
Promoter Regions ◽  
Modern Biology ◽  
Genome Wide ◽  
Urgent Task ◽  
Expression Atlas ◽  
Expression Activity

Creating a complete picture of the regulation of transcription seems to be an urgent task of modern biology. Regulation of transcription is a complex process carried out by transcription factors (TFs) and auxiliary proteins. Over the past decade, ChIP-Seq has become the most common experimental technology studying genome-wide interactions between TFs and DNA. We assessed the transcriptional significance of cell line-specific features using regression analysis of ChIP-Seq datasets from the GTRD database and transcriptional start site (TSS) activities from the FANTOM5 expression atlas. For this purpose, we initially generated a large number of features that were defined as the presence or absence of TFs in different promoter regions around TSSs. Using feature selection and regression analysis, we identified sets of the most important TFs that affect expression activity of TSSs in human cell lines such as HepG2, K562 and HEK293. We demonstrated that some TFs can be classified as repressors and activators depending on their location relative to TSS.

scholarly journals Genome-Wide Identification of GDSL-Type Esterase/Lipase Gene Family in Dasypyrum villosum L. Reveals That DvGELP53 Is Related to BSMV Infection

2021 ◽  
Vol 22 (22) ◽  
pp. 12317
Author(s):  
Heng Zhang ◽  
Xu Zhang ◽  
Jia Zhao ◽  
Li Sun ◽  
Haiyan Wang ◽  
...  
Keyword(s):  
Plant Growth ◽  
Gene Family ◽  
Dasypyrum Villosum ◽  
Promoter Regions ◽  
Lipase Gene ◽  
Long Distance ◽  
Enzyme Superfamily ◽  
Genome Wide ◽  
A Genome ◽  
Long Distance Movement

GDSL-type esterase/lipase proteins (GELPs) characterized by a conserved GDSL motif at their N-terminus belong to the lipid hydrolysis enzyme superfamily. In plants, GELPs play an important role in plant growth, development and stress response. The studies of the identification and characterization of the GELP gene family in Triticeae have not been reported. In this study, 193 DvGELPs were identified in Dasypyrum villosum and classified into 11 groups (clade A–K) by means of phylogenetic analysis. Most DvGELPs contain only one GDSL domain, only four DvGELPs contain other domains besides the GDSL domain. Gene structure analysis indicated 35.2% DvGELP genes have four introns and five exons. In the promoter regions of the identified DvGELPs, we detected 4502 putative cis-elements, which were associated with plant hormones, plant growth, environmental stress and light responsiveness. Expression profiling revealed 36, 44 and 17 DvGELPs were highly expressed in the spike, the root and the grain, respectively. Further investigation of a root-specific expressing GELP, DvGELP53, indicated it was induced by a variety of biotic and abiotic stresses. The knockdown of DvGELP53 inhibited long-distance movement of BSMV in the tissue of D. villosum. This research provides a genome-wide glimpse of the D. villosum GELP genes and hints at the participation of DvGELP53 in the interaction between virus and plants.

scholarly journals Restricted nucleation and piRNA-mediated establishment of heterochromatin during embryogenesis in Drosophila miranda

2021 ◽  
Author(s):  
Kevin H.-C. Wei ◽  
Carolus Chan ◽  
Doris Bachtrog
Keyword(s):  
Genome Stability ◽  
Repetitive Sequences ◽  
Developmental Time ◽  
Wide Distribution ◽  
Promoter Regions ◽  
Architectural Feature ◽  
Genome Wide ◽  
Nucleation Sites ◽  
Zygotic Transcription ◽  
Initial Nucleation

Heterochromatin is a key architectural feature of eukaryotic genomes, crucial for silencing of repetitive elements and maintaining genome stability. Heterochromatin shows stereotypical enrichment patterns around centromeres and repetitive sequences, but the molecular details of how heterochromatin is established during embryogenesis are poorly understood. Here, we map the genome-wide distribution of H3K9me3-dependent heterochromatin in individual embryos of D. miranda at precisely staged developmental time points. We find that canonical H3K9me3 enrichment patterns are established early on before cellularization, and mature into stable and broad heterochromatin domains through development. Intriguingly, initial nucleation sites of H3K9me3 enrichment appear as early as embryonic stage3 (nuclear cycle 9) over transposable elements (TE) and progressively broaden, consistent with spreading to neighboring nucleosomes. The earliest nucleation sites are limited to specific regions of a small number of TE families and often appear over promoter regions, while late nucleation develops broadly across most TEs. Early nucleating TEs are highly targeted by maternal piRNAs and show early zygotic transcription, consistent with a model of co-transcriptional silencing of TEs by small RNAs. Interestingly, truncated TE insertions lacking nucleation sites show significantly reduced enrichment across development, suggesting that the underlying sequences play an important role in recruiting histone methyltransferases for heterochromatin establishment.

scholarly journals Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome

2018 ◽  
Vol 115 (15) ◽  
pp. E3408-E3415 ◽  
Author(s):  
Wentao Li ◽  
Ogun Adebali ◽  
Yanyan Yang ◽  
Christopher P. Selby ◽  
Aziz Sancar
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Excision Repair ◽  
Model Organism ◽  
Early Time ◽  
Uv Damage ◽  
Single Nucleotide ◽  
Pyrimidine Dimers ◽  
Genome Wide ◽  
Nucleotide Resolution ◽  
Single Nucleotide Resolution

We have adapted the eXcision Repair-sequencing (XR-seq) method to generate single-nucleotide resolution dynamic repair maps of UV-induced cyclobutane pyrimidine dimers and (6-4) pyrimidine–pyrimidone photoproducts in the Saccharomyces cerevisiae genome. We find that these photoproducts are removed from the genome primarily by incisions 13–18 nucleotides 5′ and 6–7 nucleotides 3′ to the UV damage that generate 21- to 27-nt-long excision products. Analyses of the excision repair kinetics both in single genes and at the genome-wide level reveal strong transcription-coupled repair of the transcribed strand at early time points followed by predominantly nontranscribed strand repair at later stages. We have also characterized the excision repair level as a function of the transcription level. The availability of high-resolution and dynamic repair maps should aid in future repair and mutagenesis studies in this model organism.

TRIM28 maintains genome imprints and regulates development of porcine SCNT embryos

Reproduction ◽  
2021 ◽  
Vol 161 (4) ◽  
pp. 411-424
Author(s):  
Yanhui Zhai ◽  
Meng Zhang ◽  
Xinglan An ◽  
Sheng Zhang ◽  
Xiangjie Kong ◽  
...  
Keyword(s):  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Transcript Abundance ◽  
Dna Demethylation ◽  
Epigenetic Variability ◽  
Promoter Regions ◽  
Cell Stage ◽  
Genome Wide ◽  
Developmental Progression ◽  
Imprinting Gene

Pre-implantation embryos undergo genome-wide DNA demethylation, however certain regions, like imprinted loci remain methylated. Further, the mechanisms ensuring demethylation resistance by TRIM28 in epigenetic reprogramming remain poorly understood. Here, TRIM28 was knocked down in oocytes, and its effects on porcine somatic cell nuclear transfer (SCNT) embryo development was examined. Our results showed that SCNT embryos constructed from TRIM28 knockdown oocytes had significantly lower cleavage (53.9 ± 3.4% vs 64.8 ± 2.7%) and blastocyst rates (12.1 ± 4.3% vs 19.8 ± 1.9%) than control-SCNT embryos. The DNA methylation levels at the promoter regions of the imprinting gene IGF2 and H19 were significantly decreased in the 4-cell stage, and the transcript abundance of other imprinting gene was substantially increased. We also identified an aberrant two-fold decrease in the expression of CXXC1and H3K4me3 methyltransferase (ASH2L and MLL2), and the signal intensity of H3K4me3 had a transient drop in SCNT 2-cell embryos. Our results indicated that maternal TRIM28 knockdown disrupted the genome imprints and caused epigenetic variability in H3K4me3 levels, which blocked the transcription activity of zygote genes and affected the normal developmental progression of porcine SCNT embryos.

Sign in / Sign up

Export Citation Format

Share Document