scholarly journals Insulator proteins contribute to expression of gene loci repositioned into heterochromatin in the course of Drosophila evolution

2019 ◽  
Author(s):  
Sergei Yu. Funikov ◽  
Alexander P. Rezvykh ◽  
Dina A. Kulikova ◽  
Elena S. Zelentsova ◽  
Lyubov N. Chuvakova ◽  
...  

AbstractPericentric heterochromatin in Drosophila is generally composed of repetitive DNA forming a transcriptionally repressive environment. Nevertheless, dozens of genes were embedded into pericentric genome regions during evolution of Drosophilidae lineage and retained functional activity. However, factors that contribute to “immunity” of these gene loci to transcriptional silencing remain unknown. Here, we investigated molecular evolution of the essential Myb and Ranbp16 genes. These protein-coding genes reside in euchromatic loci of chromosome X in D. melanogaster and related species, while in other studied Drosophila species, including evolutionary distant ones, they are located in genomic regions highly enriched with the remnants of transposable elements (TEs), suggesting their heterochromatic nature and location. The promoter region of Myb exhibits a conserved structure throughout the Drosophila phylogeny and carries motifs for binding of chromatin remodeling factors, including insulator BEAF-32, regardless of eu- or heterochromatic surroundings. Importantly, BEAF-32 occupies not only the promoter region of Myb but is also found in the vicinity of transcriptional start sites (TSS) of Ranbp16 gene as well as in a wide range of genes located in the contrasting chromatin types in D. melanogaster and D. virilis, denoting the boundary of the nucleosome-free region available for RNA polymerase II recruitment and the surrounding heterochromatin. We also find that along with BEAF-32, insulators dCTCF and GAF are enriched at the TSS of heterochromatic genes in D. melanogaster. Thus, we propose that insulator proteins contribute to gene expression in the heterochromatic environment and, hence, facilitate the evolutionary repositioning of gene loci into heterochromatin.Author summaryHeterochromatin in Drosophila is generally associated with transcriptional silencing. Nevertheless, hundreds of essential genes have been identified in the pericentric heterochromatin of Drosophila melanogaster. Interestingly, genes embedded in pericentric heterochromatin of D. melanogaster may occupy different genomic loci, euchromatic or heterochromatic, due to repositioning in the course of evolution of Drosophila species. By surveying factors that contribute to the normal functioning of the relocated genes in distant Drosophila species, i.e. D. melanogaster and D. virilis, we identify certain insulator proteins (e.g.BEAF-32) that facilitate the expression of heterochromatic genes in spite of the repressive environment.


2013 ◽  
Vol 103 (5) ◽  
pp. 479-487 ◽  
Author(s):  
Efrén Remesal ◽  
Blanca B. Landa ◽  
María del Mar Jiménez-Gasco ◽  
Juan A. Navas-Cortés

Populations of Sclerotium rolfsii, the causal organism of Sclerotium root-rot on a wide range of hosts, can be placed into mycelial compatibility groups (MCGs). In this study, we evaluated three different molecular approaches to unequivocally identify each of 12 previously identified MCGs. These included restriction fragment length polymorphism (RFLP) patterns of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (rDNA) and sequence analysis of two protein-coding genes: translation elongation factor 1α (EF1α) and RNA polymerase II subunit two (RPB2). A collection of 238 single-sclerotial isolates representing 12 MCGs of S. rolfsii were obtained from diseased sugar beet plants from Chile, Italy, Portugal, and Spain. ITS-RFLP analysis using four restriction enzymes (AluI, HpaII, RsaI, and MboI) displayed a low degree of variability among MCGs. Only three different restriction profiles were identified among S. rolfsii isolates, with no correlation to MCG or to geographic origin. Based on nucleotide polymorphisms, the RPB2 gene was more variable among MCGs compared with the EF1α gene. Thus, 10 of 12 MCGs could be characterized utilizing the RPB2 region only, while the EF1α region resolved 7 MCGs. However, the analysis of combined partial sequences of EF1α and RPB2 genes allowed discrimination among each of the 12 MCGs. All isolates belonging to the same MCG showed identical nucleotide sequences that differed by at least in one nucleotide from a different MCG. The consistency of our results to identify the MCG of a given S. rolfsii isolate using the combined sequences of EF1α and RPB2 genes was confirmed using blind trials. Our study demonstrates that sequence variation in the protein-coding genes EF1α and RPB2 may be exploited as a diagnostic tool for MCG typing in S. rolfsii as well as to identify previously undescribed MCGs.



MicroRNA ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 93-100 ◽  
Author(s):  
Rabih Roufayel ◽  
Seifedine kadry

Background: Signaling pathways including gene silencing, cellular differentiation, homeostasis, development and apoptosis are regulated and controlled by a wide range of miRNAs. Objective: Due to their potential binding sites in human-protein coding genes, many studies have also linked their altered expressions in various cancer types making them tumor suppressors agents. Methods: Moreover, each miRNA is predicted to have many mRNA targets indicating their extensive regulatory role in cell survival and developmental processes. Nowadays, diagnosis of early cancer stage development is now dependent on variable miRNA expression levels as potential oncogenic biomarkers in validating and targeting microRNAs for cancer therapy. Results: As the majority of miRNA, transcripts are derived from RNA polymerase II-directed transcription, stress response could result on a general reduction in the abundance of these transcripts. Over expression of various microRNAs have lead to B cell malignancy, potentiated KrasG12Dinduced lung tumorigenesis, chronic lymphocytic leukemia, lymphoproliferative disease and autoimmunity. Conclusion: Altered miRNA expressions could have a significant impact on the abundance of proteins, making them attractive candidates as biomarkers for cancer detection and important regulators of apoptosis.



1999 ◽  
Vol 73 (10) ◽  
pp. 8741-8749 ◽  
Author(s):  
Juhana Santti ◽  
Timo Hyypiä ◽  
Leena Kinnunen ◽  
Mika Salminen

ABSTRACT Human enteroviruses consist of more than 60 serotypes, reflecting a wide range of evolutionary divergence. They have been genetically classified into four clusters on the basis of sequence homology in the coding region of the single-stranded RNA genome. To explore further the genetic relationships between human enteroviruses and to characterize the evolutionary mechanisms responsible for variation, previously sequenced genomes were subjected to detailed comparison. Bootstrap and genetic similarity analyses were used to systematically scan the alignments of complete genomic sequences. Bootstrap analysis provided evidence from an early recombination event at the junction of the 5′ noncoding and coding regions of the progenitors of the current clusters. Analysis within the genetic clusters indicated that enterovirus prototype strains include intraspecies recombinants. Recombination breakpoints were detected in all genomic regions except the capsid protein coding region. Our results suggest that recombination is a significant and relatively frequent mechanism in the evolution of enterovirus genomes.



2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xuhong Yu ◽  
Pascal G. P. Martin ◽  
Scott D. Michaels

Abstract Ensuring that one gene’s transcription does not inappropriately affect the expression of its neighbors is a fundamental challenge to gene regulation in a genomic context. In plants, which lack homologs of animal insulator proteins, the mechanisms that prevent transcriptional interference are not well understood. Here we show that BORDER proteins are enriched in intergenic regions and prevent interference between closely spaced genes on the same strand by promoting the 3′ pausing of RNA polymerase II at the upstream gene. In the absence of BORDER proteins, 3′ pausing associated with the upstream gene is reduced and shifts into the promoter region of the downstream gene. This is consistent with a model in which BORDER proteins inhibit transcriptional interference by preventing RNA polymerase from intruding into the promoters of downstream genes.



2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hrant Hovhannisyan ◽  
Toni Gabaldón

AbstractLong non-coding RNAs (lncRNAs) constitute a poorly studied class of transcripts with emerging roles in key cellular processes. Despite efforts to characterize lncRNAs across a wide range of species, these molecules remain largely unexplored in most eukaryotic microbes, including yeast pathogens of the Candida clade. Here, we analyze thousands of publicly available sequencing datasets to infer and characterize the lncRNA repertoires of five major Candida pathogens: Candida albicans, Candida tropicalis, Candida parapsilosis, Candida auris and Candida glabrata. Our results indicate that genomes of these species encode hundreds of lncRNAs that show levels of evolutionary constraint intermediate between those of intergenic genomic regions and protein-coding genes. Despite their low sequence conservation across the studied species, some lncRNAs are syntenic and are enriched in shared sequence motifs. We find co-expression of lncRNAs with certain protein-coding transcripts, hinting at potential functional associations. Finally, we identify lncRNAs that are differentially expressed during infection of human epithelial cells for four of the studied species. Our comprehensive bioinformatic analyses of Candida lncRNAs pave the way for future functional characterization of these transcripts.



2020 ◽  
Author(s):  
Wim J. de Jonge ◽  
Mariël Brok ◽  
Philip Lijnzaad ◽  
Patrick Kemmeren ◽  
Frank C.P. Holstege

AbstractProtein-DNA interactions are dynamic and these dynamics are an important aspect of chromatin-associated processes such as transcription or replication. Due to a lack of methods to study on- and off-rates across entire genomes, protein-DNA interaction dynamics have not been studied extensively. Here we determine in vivo off-rates for the Saccharomyces cerevisiae chromatin organising factor Abf1, at 191 sites simultaneously across the yeast genome. Average Abf1 residence times span a wide-range, varying between 4.5 and 37 minutes. Sites with different off-rates are associated with different functional characteristics. This includes their transcriptional dependency on Abf1, nucleosome positioning and the size of the nucleosome-free region, as well as the ability to roadblock RNA polymerase II for termination. The results show how off-rates contribute to transcription factor function and that DIVORSEQ (Determining In Vivo Off-Rates by SEQuencing) is a meaningful way of investigating protein-DNA binding dynamics genome-wide.



2021 ◽  
Vol 7 (3) ◽  
pp. 42
Author(s):  
Victoria Mamontova ◽  
Barbara Trifault ◽  
Lea Boten ◽  
Kaspar Burger

Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.



2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Suzanne V Saenko ◽  
Dick S J Groenenberg ◽  
Angus Davison ◽  
Menno Schilthuizen

Abstract Studies on the shell color and banding polymorphism of the grove snail Cepaea nemoralis and the sister taxon Cepaea hortensis have provided compelling evidence for the fundamental role of natural selection in promoting and maintaining intraspecific variation. More recently, Cepaea has been the focus of citizen science projects on shell color evolution in relation to climate change and urbanization. C. nemoralis is particularly useful for studies on the genetics of shell polymorphism and the evolution of “supergenes,” as well as evo-devo studies of shell biomineralization, because it is relatively easily maintained in captivity. However, an absence of genomic resources for C. nemoralis has generally hindered detailed genetic and molecular investigations. We therefore generated ∼23× coverage long-read data for the ∼3.5 Gb genome, and produced a draft assembly composed of 28,537 contigs with the N50 length of 333 kb. Genome completeness, estimated by BUSCO using the metazoa dataset, was 91%. Repetitive regions cover over 77% of the genome. A total of 43,519 protein-coding genes were predicted in the assembled genome, and 97.3% of these were functionally annotated from either sequence homology or protein signature searches. This first assembled and annotated genome sequence for a helicoid snail, a large group that includes edible species, agricultural pests, and parasite hosts, will be a core resource for identifying the loci that determine the shell polymorphism, as well as in a wide range of analyses in evolutionary and developmental biology, and snail biology in general.



2013 ◽  
Vol 4 (1) ◽  
pp. 32 ◽  
Author(s):  
Dmitry Velmeshev ◽  
Marco Magistri ◽  
Mohammad Faghihi


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