Open Chromatin Analysis in Trypanosoma Cruzi Life Forms Highlights Critical Differences in Genomic Compartments and Developmental Regulation at tDNA Loci

Abstract Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.

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Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci

10.1101/2021.10.26.465934 ◽

2021 ◽

Author(s):

Alex RJ Lima ◽

Saloe B Poubel ◽

Juliana N Roson ◽

Loyze PO de Lima ◽

Hellida M Costa-Silva ◽

...

Keyword(s):

Gene Expression ◽

Trypanosoma Cruzi ◽

Gene Expression Regulation ◽

Gene Clusters ◽

Expression Regulation ◽

Open Chromatin ◽

Protein Coding ◽

Posttranscriptional Control ◽

Protein Coding Genes ◽

The Impact

Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.

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GC-AG introns features in long non-coding and protein-coding genes suggest their role in gene expression regulation

10.26226/morressier.5ebd45acffea6f735881b039 ◽

2020 ◽

Author(s):

Monah Abou Alezz

Keyword(s):

Gene Expression ◽

Gene Expression Regulation ◽

Expression Regulation ◽

Protein Coding ◽

Protein Coding Genes

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GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation

Frontiers in Genetics ◽

10.3389/fgene.2020.00488 ◽

2020 ◽

Vol 11 ◽

Author(s):

Monah Abou Alezz ◽

Ludovica Celli ◽

Giulia Belotti ◽

Antonella Lisa ◽

Silvia Bione

Keyword(s):

Gene Expression ◽

Gene Expression Regulation ◽

Expression Regulation ◽

Protein Coding ◽

Protein Coding Genes

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GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation

10.1101/683938 ◽

2019 ◽

Author(s):

Monah Abou Alezz ◽

Ludovica Celli ◽

Giulia Belotti ◽

Antonella Lisa ◽

Silvia Bione

Keyword(s):

Gene Expression Regulation ◽

Expression Regulation ◽

Splice Sites ◽

Protein Coding ◽

Protein Coding Genes ◽

First Intron ◽

Genes Expression ◽

Donor And Acceptor ◽

Significant Enrichment ◽

Splice Junctions

ABSTRACTLong non-coding RNAs (lncRNAs) are recognized as an important class of regulatory molecules involved in a variety of biological functions. However, the regulatory mechanisms of long non-coding genes expression are still poorly understood. The characterization of the genomic features of lncRNAs is crucial to get insight into their function. In this study, we exploited recent annotations by GENCODE to characterize the genomic and splicing features of long non-coding genes in comparison with protein-coding ones, both in human and mouse. Our analysis highlighted differences between the two classes of genes in terms of their gene architecture. Significant differences in the splice sites usage were observed between long non-coding and protein-coding genes (PCG). While the frequency of non-canonical GC-AG splice junctions represents about 0.8% of total splice sites in PCGs, we identified a significant enrichment of the GC-AG splice sites in long non-coding genes, both in human (3.0%) and mouse (1.9%). In addition, we found a positional bias of GC-AG splice sites being enriched in the first intron in both classes of genes. Moreover, a significant shorter length and weaker donor and acceptor sites were found comparing GC-AG introns to GT-AG introns. Genes containing at least one GC-AG intron were found conserved in many species, more prone to alternative splicing and a functional analysis pointed toward their enrichment in specific biological processes such as DNA repair. Our study shows for the first time that GC-AG introns are mainly associated with lncRNAs and are preferentially located in the first intron. Additionally, we discovered their regulatory potential indicating the existence of a new mechanism of non-coding and PCGs expression regulation.

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Functional and transcriptional profiling of non-coding RNAs in yeast reveal context-dependent phenotypes and widespread in trans effects on the protein regulatory network

10.1101/2020.04.07.029611 ◽

2020 ◽

Author(s):

Laura Natalia Balarezo-Cisneros ◽

Steven Parker ◽

Marcin G Fraczek ◽

Soukaina Timouma ◽

Ping Wang ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Environmental Conditions ◽

Mode Of Action ◽

Protein Coding ◽

Protein Coding Genes ◽

Genome Wide ◽

In Trans ◽

Non Coding Rnas ◽

The Impact

AbstractNon-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response of different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT530, SUT468) or rRNA processing (SUT075 and snR30). Overall, this data captures and integrates the regulatory and phenotypic network of ncRNAs and protein coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.Author SummaryThe yeast genome contains 25% of non-coding RNA molecules (ncRNAs), which do not translate into proteins but are involved in regulation of gene expression. ncRNAs can affect nearby genes by physically interfering with their transcription (cis mode of action), or they interact with DNA, proteins or others RNAs to regulate the expression of distant genes (trans mode of action). Examples of cis-acting ncRNAs have been broadly described, however genome-wide studies to identify functional trans-acting ncRNAs involved in global gene regulation are still lacking. Here, we used the ncRNA yeast deletion collection to score their impact on cellular function in different environmental conditions. A group of 20 ncRNAs mutants with broad fitness diversity were selected to investigate their effect on the protein and ncRNA expression network. We showed a high correlation between altered phenotypes and global transcriptional changes, in an environmental dependent manner. We confirmed the widespread trans acting expressional regulation of ncRNAs in the genome and their role in affecting transcription factors. These findings support the notion of the involvement on ncRNAs in fine tuning the cellular expression via regulations of TFs, as an advantageous RNA-mediated mechanism that can be fast and cost-effective for the cells.

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Cell Biology of the Trypanosome Genome

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.00024-10 ◽

2010 ◽

Vol 74 (4) ◽

pp. 552-569 ◽

Cited By ~ 77

Author(s):

Jan-Peter Daniels ◽

Keith Gull ◽

Bill Wickstead

Keyword(s):

Gene Expression ◽

Cell Biology ◽

Nuclear Organization ◽

Nuclear Architecture ◽

Gene Clusters ◽

Model Organisms ◽

Protein Coding ◽

African Trypanosomes ◽

Protein Coding Genes ◽

A Genome

SUMMARY Trypanosomes are a group of protozoan eukaryotes, many of which are major parasites of humans and livestock. The genomes of trypanosomes and their modes of gene expression differ in several important aspects from those of other eukaryotic model organisms. Protein-coding genes are organized in large directional gene clusters on a genome-wide scale, and their polycistronic transcription is not generally regulated at initiation. Transcripts from these polycistrons are processed by global trans-splicing of pre-mRNA. Furthermore, in African trypanosomes, some protein-coding genes are transcribed by a multifunctional RNA polymerase I from a specialized extranucleolar compartment. The primary DNA sequence of the trypanosome genomes and their cellular organization have usually been treated as separate entities. However, it is becoming increasingly clear that in order to understand how a genome functions in a living cell, we will need to unravel how the one-dimensional genomic sequence and its trans-acting factors are arranged in the three-dimensional space of the eukaryotic nucleus. Understanding this cell biology of the genome will be crucial if we are to elucidate the genetic control mechanisms of parasitism. Here, we integrate the concepts of nuclear architecture, deduced largely from studies of yeast and mammalian nuclei, with recent developments in our knowledge of the trypanosome genome, gene expression, and nuclear organization. We also compare this nuclear organization to those in other systems in order to shed light on the evolution of nuclear architecture in eukaryotes.

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Uncovering divergence in gene expression regulation in the adaptation of yeast to nitrogen scarcity

10.1101/2021.04.15.440091 ◽

2021 ◽

Author(s):

Carlos A. Villarroel ◽

Paulo Canessa ◽

Macarena Bastias ◽

Francisco A Cubillos

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Gene Expression Regulation ◽

Transcription Factor Binding ◽

Chromatin Accessibility ◽

Expression Regulation ◽

Factor Binding ◽

Allele Specific ◽

The Impact ◽

Allelic Bias

Saccharomyces cerevisiae rewires its transcriptional output to survive stressful environments, such as nitrogen scarcity under fermentative conditions. Although divergence in nitrogen metabolism has been described among natural yeast populations, the impact of regulatory genetic variants modulating gene expression and nitrogen consumption remains to be investigated. Here, we employed an F1 hybrid from two contrasting S. cerevisiae strains, providing a controlled genetic environment to map cis factors involved in the divergence of gene expression regulation in response to nitrogen scarcity. We used a dual approach to obtain genome-wide allele-specific profiles of chromatin accessibility, transcription factor binding, and gene expression through ATAC-seq and RNA-seq. We observed large variability in allele-specific expression and accessibility between the two genetic backgrounds, with a third of these differences specific to a deficient nitrogen environment. Furthermore, we discovered events of allelic bias in gene expression correlating with allelic bias in transcription factor binding solely under nitrogen scarcity, where the majority of these transcription factors orchestrates the Nitrogen Catabolite Repression regulatory pathway and demonstrates a cis x environment-specific response. Our approach allowed us to find cis variants modulating gene expression, chromatin accessibility and allelic differences in transcription factor binding in response to low nitrogen culture conditions.

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RNA Binding Proteins and Gene Expression Regulation in Trypanosoma cruzi

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.00056 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 2

Author(s):

Bruno A. A. Romagnoli ◽

Fabiola B. Holetz ◽

Lysangela R. Alves ◽

Samuel Goldenberg

Keyword(s):

Gene Expression ◽

Trypanosoma Cruzi ◽

Binding Proteins ◽

Rna Binding ◽

Gene Expression Regulation ◽

Rna Binding Proteins ◽

Expression Regulation

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Effects of Mating on Gene Expression in Female Insects: Unifying the Field

Insects ◽

10.3390/insects13010069 ◽

2022 ◽

Vol 13 (1) ◽

pp. 69

Author(s):

Ferdinand Nanfack-Minkeu ◽

Laura King Sirot

Keyword(s):

Gene Expression ◽

Reproductive Output ◽

Gene Expression Regulation ◽

Seminal Fluid ◽

Expression Patterns ◽

Expression Regulation ◽

Insect Species ◽

Functional Consequences ◽

And Behavior ◽

The Impact

There is intense interest in controlling insect reproductive output. In many insect species, reproductive output is profoundly influenced by mating, including the receipt of sperm and seminal fluid molecules, through physiological and behavior changes. To understand these changes, many researchers have investigated post-mating gene expression regulation. In this review, we synthesize information from studies both across and within different species about the impact of mating, or components of mating, on female gene expression patterns. We found that genes related to the roles of metabolism, immune-response, and chemosensation are regulated by mating across many different insect species. We highlight the few studies that have taken the important next step of examining the functional consequences of gene expression regulation which is crucial in order to understand the mechanisms underlying the mating-regulated control of female lifespan and reproduction and to make use of such knowledge to propagate or control insect populations. The potential of cross-study comparisons is diminished by different studies using different methods. Thus, we also include a consideration of how future studies could be designed to facilitate cross-study comparisons and a call for collaboration across researchers studying different insect species and different aspects of insect biology.

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