Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dissecting the Roles of Divergent and Convergent Transcription in Chromosome Instability.

ABSTRACT: The interplay of transcription, topological tension, and chromosome breakage is a subject of intense interest, but, with so many facets to the problem, it is difficult to test. Here, we vary the orientation of promoters relative to one another in a yeast system that permits sensitive detection of chromosome breaks. Interestingly, convergent transcription that would direct RNA polymerases into one another does not increase chromosome breakage. In contrast, divergent transcription that would create underwound and potentially single-stranded DNA does cause a marked increase in chromosome breakage. Furthermore, we examine the role that topoisomerases are playing in preventing genome instability at these promoters and find that Top2 is required to prevent instability at converging promoters.

SUBMITTER: Pannunzio NR

PROVIDER: S-EPMC6028021 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Dissecting the Roles of Divergent and Convergent Transcription in Chromosome Instability.

Pannunzio Nicholas R NR Lieber Michael R MR

Cell reports 20160121 5

The interplay of transcription, topological tension, and chromosome breakage is a subject of intense interest, but, with so many facets to the problem, it is difficult to test. Here, we vary the orientation of promoters relative to one another in a yeast system that permits sensitive detection of chromosome breaks. Interestingly, convergent transcription that would direct RNA polymerases into one another does not increase chromosome breakage. In contrast, divergent transcription that would creat ...[more]

PMID: 26804908

Similar Datasets

Dissecting comimetic radiations in Heliconius reveals divergent histories of convergent butterflies.

Project description:Mimicry among Heliconius butterflies provides a classic example of coevolution but unresolved relationships among mimetic subspecies have prevented examination of codiversification between species. We present amplified fragment length polymorphism and mtDNA datasets for the major comimetic races of Heliconius erato and H. melpomene. The AFLP data reveal unprecedented resolution, clustering samples by geography and race in both species. Our results show that, although H. erato and H. melpomene co-occur, mimic each other, and exhibit parallel shifts in color pattern, they experienced very different modes of diversification and geographic histories. Our results suggest that H. erato originated on the western side of South America whereas H. melpomene originated in the east. H. erato underwent rapid diversification and expansion with continued gene-flow following diversification, resulting in widely dispersed sister taxa. In contrast, H. melpomene underwent a slower pace of diversification with lower levels of gene flow, producing a stepwise directional expansion from west to east. Our results also suggest that each of the three main wing pattern phenotypes originated and/or was lost multiple times in each species. The rayed pattern is likely to be the ancestral phenotype in H. erato whereas postman or red patch is likely to be ancestral in H. melpomene. Finally, H. cydno and H. himera are monophyletic entities clearly nested within H. melpomene and H. erato, rather than being their respective sister species. Estimates of mtDNA divergence suggest a minimum age of 2.8 and 2.1 My for H. erato and H. melpomene, respectively, placing their origins in the late Pliocene.

| S-EPMC2867687 | biostudies-literature

Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability.

Project description:Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single-stranded DNA targets. Though largely specific for immunoglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing mystery. Based on deep GRO-seq studies of mouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target translocations occur within highly focal regions of target genes in which sense and antisense transcription converge. Moreover, we found that such AID-targeting "convergent" transcription arises from antisense transcription that emanates from super-enhancers within sense transcribed gene bodies. Our findings provide an explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells.

| S-EPMC4322776 | biostudies-literature

Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development.

Project description:Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex chromosome aneuploidies (SCAs). We show that X- and Y-chromosomes have opposing effects on overall brain size but exert highly convergent influences on local brain anatomy, which manifest across biologically distinct dimensions of the cerebral cortex. Large-scale online meta-analysis of functional neuroimaging data indicates that convergent sex chromosome dosage effects preferentially impact centers for social perception, communication, and decision-making. Thus, despite an almost complete lack of sequence homology, and opposing effects on overall brain size, X- and Y-chromosomes exert congruent effects on the proportional size of cortical systems involved in adaptive social functioning. These convergent X-Y effects (i) track the dosage of those few genes that are still shared by X- and Y-chromosomes, and (ii) may provide a biological substrate for the link between SCA and increased rates of psychopathology.

| S-EPMC4701121 | biostudies-literature

Chromosomal instability drives convergent and divergent evolution toward advantageous inherited traits in mammalian CHO bioproduction lineages.

Project description:Genetic instability of Chinese hamster ovary (CHO) cells is implicated in production inconsistency through poorly defined mechanisms. Using a multi-omics approach, we analyzed the variations of CHO lineages derived from CHO-K1 cells. We identify an equilibrium between random genetic variation of the CHO genome and heritable traits driven by culture conditions, selection criteria, and genetic linkage. These inherited changes are associated with the selection pressures related to serum removal, suspension culture transition, protein expression, and secretion. We observed that a haploid reduction of a Chromosome 2 region after serum-free, suspension adaptation, was consistently inherited, suggesting common adaptation mechanisms. Genetic variations also included ∼200 insertions/deletions, ∼1000 single-nucleotide polymorphisms, and ∼300-2000 copy number variations, which were exacerbated after gene editing. In addition, heterochromatic chromosomes were preferentially lost as cells continuously evolved. Together, these observations demonstrate a highly plastic signature for adapted CHO cells and paves the way towards future host cell engineering.

| S-EPMC8958363 | biostudies-literature

A case of convergent-gene interference in the budding yeast knockout library causing chromosome instability.

Project description:To maintain genome stability, organisms depend on faithful chromosome segregation, a process affected by diverse genetic pathways, some of which are not directly linked to mitosis. In this study, we set out to explore one such pathway represented by an undercharacterized gene, SNO1, identified previously in screens of the yeast knockout (YKO) library for mitotic fidelity genes. We found that the causative factor increasing mitotic error rate in the sno1Δ mutant is not loss of the Sno1 protein, but rather perturbation to the mRNA of the neighboring convergent gene, CTF13, encoding an essential component for forming the yeast kinetochore. This is caused by a combination of the Kanamycin resistance gene and the transcriptional terminator used in the YKO library affecting the CTF13 mRNA level and quality . We further provide a list of gene pairs potentially subjected to this artifact, which may be useful for accurate phenotypic interpretation of YKO mutants.

| S-EPMC8104933 | biostudies-literature

Divergent and Convergent Evolution of Fungal Pathogenicity.

Project description:Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen-host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus-animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation.

| S-EPMC4898799 | biostudies-other

Topological constraints impair RNA polymerase II transcription and causes instability of plasmid-borne convergent genes.

Project description:Despite the theoretical bases for the association of topoisomerases and supercoiling changes with transcription and replication, our knowledge of the impact of topological constraints on transcription and replication is incomplete. Although mutation of topoisomerases affects expression and stability of the rDNA region it is not clear whether the same is the case for RNAPII transcription and genome integrity in other regions. We developed new assays in which two convergent RNAPII-driven genes are transcribed simultaneously. Plasmid-based systems were constructed with and without a transcription terminator between the two convergent transcription units, so that the impact of transcription interference could also be evaluated. Using these assays we show that Topos I and II play roles in RNAPII transcription in vivo and reduce the stability of RNAPII-transcribed genes in Saccharomyces cerevisiae. Supercoiling accumulation in convergent transcription units impairs RNAPII transcription in top1? strains, but Topo II is also required for efficient transcription independent of Topo I and of detectable supercoiling accumulation. Our work shows that topological constraints negatively affect RNAPII transcription and genetic integrity, and provides an assay to study gene regulation by transcription interference.

| S-EPMC3273821 | biostudies-other

Chromosome instability caused by mutations in the genes involved in transcription and splicing.

Project description:Mutations in molecules involved in transcription and splicing can cause chromosome instability such as sister chromatid exchanges. We isolated and characterized responsible genes from mammalian temperature-sensitive mutant cells showing chromosome instability. A mutation in the largest subunit of RNA polymerase II affected DNA synthesis in S phase-arrested cells, resulting in abnormal induction of sister chromatid exchanges. The yeast mutant harboring a homologous mutation showed very similar phenotype to that of the mammalian mutant. A mutation in Smu1, which is involved in splicing, also affected DNA synthesis in S and G2 phase-arrested cells, resulting in abnormal induction of sister chromatid exchanges and chromosomal aberrations. These cells showed a connection between defects of RNA metabolism and induction of chromosome instability. Genome instability appeared to be caused by links between RNA metabolism and replication resulting in genomic recombination. RNA metabolism can be regarded as one possible driver of genome modification triggering genome evolution.

| S-EPMC6779378 | biostudies-literature

Chromosome instability caused by mutations in the genes involved in transcription and splicing.

| S-EPMC6779378 | biostudies-literature

Convergent Sense/Antisense Transcription At Intragenic Super-Enhancers Targets AID-initiated Genomic Instability

Project description:Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) for antibody affinity maturation and DNA breakage for antibody class switch recombination (CSR) via transcription-dependent cytidine deamination of single stranded DNA targets. While largely specific for immunglobulin genes, AID also acts on a limited set of off-targets, generating oncogenic translocations and mutations that contribute to B cell lymphoma. How AID is recruited to off-targets has been a long-standing mystery. Based on deep GRO-Seq studies of mouse and human B lineage cells activated for CSR or SHM, we report that most robust AID off-target translocations occur within highly focal regions of target genes in which sense and antisense transcription converge. Moreover, we found that such AID-targeting "convergent" transcription arises from antisense transcription that emanates from Super-Enhancers within sense transcribed gene bodies. Our findings provide a mechanistic explanation for AID off-targeting to a small subset of mostly lineage-specific genes in activated B cells.

2014-12-04 | GSE62296 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data