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Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells

ABSTRACT: Transcriptional regulatory changes have been shown to contribute to phenotypic differences between species, but many questions remain about how gene expression evolves. Here we report the first comparative study of nascent transcription in primates. We used PRO-seq to map actively transcribing RNA polymerases in resting and activated CD4+ T-cells in multiple human, chimpanzee, and rhesus macaque individuals, with rodents as outgroups. This approach allowed us to directly measure active transcription separately from post-transcriptional processes. We observed general conservation in coding and non-coding transcription, punctuated by numerous differences between species, particularly at distal enhancers and non-coding RNAs. Transcription factor binding sites are a primary determinant of transcriptional differences between species. We found evidence for stabilizing selection on gene expression levels and adaptive substitutions associated with lineage-specific transcription. Finally, rates of evolutionary change are strongly correlated with long-range chromatin interactions. These observations clarify the role of primary transcription in regulatory evolution.

OTHER RELATED OMICS DATASETS IN: PRJNA338193

ORGANISM(S): Mus musculus Rattus norvegicus Pan troglodytes Homo sapiens Macaca mulatta

PROVIDER: GSE85337 | GEO | 2016/12/29

SECONDARY ACCESSION(S): PRJNA338193

REPOSITORIES: GEO

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Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells

Project description:Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells

| PRJNA338193 | ENA

Non-coding RNAs Activated in Hepatoblastoma

Project description:<p>Hepatoblastoma (HB) is the most common pediatric liver tumor, affecting mostly children under 3 years of age. This rare tumor represents 1% of all pediatric cancers. Genetic studies have shown that HB is characterized by high frequency mutations of the CTNNB1 gene encoding beta-catenin (around 75%) and relative genomic stability. Here we have analyzed the transcriptional profile of 21 HBs compared to matched non-tumor livers by Cap Analysis of Gene Expression (CAGE), which provides accurate and quantitative profiling of all transcripts. CAGE analysis revealed strong upregulation of known Wnt target coding genes in most tumors analyzed, consistent with previous transcriptomic studies. To better define the Wnt-dependent transcriptional landscape of HB, we integrated CAGE data with TCF4 ChIP-seq data from a CTNNB1-mutated cancer cell line and with the FANTOM5 genomic coordinates of TCF/LEF binding motifs. Both TCF/LEF binding motifs and ChIP-seq peaks were strongly enriched in the immediate upstream region, not only for protein-coding genes, but also for non-coding transcripts. Among the selected 112 top Wnt target genes at FDR<1.0E-6 and fold change>8, we found clear over-representation (66%) of distant transcription start sites (TSSs) representing lncRNAs and enhancer RNAs, which raises the question of their role in HB pathogenesis. Analysis of the 112 promoters using CAGEd-oPOSSUM confirmed the predominant involvement of Tcf/Lef transcription factors, together with HNF4G, GATA2, Sox3 and Ets-related genes. Finally, the 112 Wnt target signature defined 3 tumor subclasses, T1, T2 and T3, characterized by progressive alteration of the non-coding part of the transcriptome and significant differences in clinical behavior.</p>

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Comprehensive Identification of Soybean Long Non-coding RNAs Reveals a Subset of Small Peptide-Coding Transcripts

Project description:Long non-coding RNAs (lncRNAs) are defined as non-protein-coding transcripts that are at least 200 nucleotides long. They are known to play pivotal roles in regulating gene expression, especially during stress responses in plants. We used a large collection of in-house transcriptome data from various soybean (Glycine max and Glycine soja) tissues treated under different conditions to perform a comprehensive identification of soybean lncRNAs. We also retrieved publicly available soybean transcriptome data that were of sufficient quality and sequencing depth to enrich our analysis. In total, RNA-seq data of 332 samples were used for this analysis. An integrated reference-based, de novo transcript assembly was developed that identified ~69,000 lncRNA gene loci. We showed that lncRNAs are distinct from both protein-coding transcripts and genomic background noise in terms of length, number of exons, transposable element composition, and sequence conservation level across legume species. The tissue-specific and time-specific transcriptional responses of the lncRNA genes under some stress conditions may suggest their biological relevance. The transcription start sites of lncRNA gene loci tend to be close to their nearest protein-coding genes, and they may be transcriptionally related to the protein-coding genes, particularly for antisense and intronic lncRNAs. A previously unreported subset of small peptide-coding transcripts was identified from these lncRNA loci via tandem mass spectrometry, which paved the way for investigating their functional roles. Our results also highlight the current inadequacy of the bioinformatic definition of lncRNA, which excludes those lncRNA gene loci with small open reading frames (ORFs) from being regarded as protein-coding.

2020-01-09 | PXD014553 | Pride

Integrative classification of human coding and non-coding genes based on RNA metabolism profiles

Project description:The pervasive transcription of the human genome results in a heterogeneous mix of coding and long non-coding RNAs (lncRNAs). Only a small fraction of lncRNAs possess demonstrated regulatory functions, making it difficult to distinguish functional lncRNAs from non-functional transcriptional byproducts. This has resulted in numerous competing incoherent annotations of human lncRNA. To address these challenges, we quantitatively examined transcription, splicing, degradation, localization and translation for coding and non-coding human genes. Annotated lncRNAs had lower synthesis and higher degradation rates than mRNAs. We discovered mechanistic differences explaining the slower splicing of lncRNAs. We grouped genes into coherent classes by performing annotation-agnostic unsupervised classification of RNA metabolism profiles. These classes contained both mRNAs and lncRNAs to varying degrees; they exhibited distinct relationships between steps of RNA metabolism, evolutionary patterns, and sensitivity to cellular RNA regulatory pathways. Our classification provides a functionally coherent alternative to genomic context-driven annotations of lncRNAs.

2016-11-04 | GSE84722 | GEO

Reinforcement of transcriptional silencing by a positive feedback between DNA methylation and non-coding transcription

Project description:Reinforcement of transcriptional silencing by a positive feedback between DNA methylation and non-coding transcription

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Olfactory receptor mRNAs act as selfish non-coding RNAs that enforce transcriptional singularity (Non-coding OR Hi-C & RNA-seq)

Project description:To investigate roles for olfactory receptor coding sequence mRNA in trans olfactory receptor gene silencing, and OR-gene enhancer recruitment. Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, as every olfactory neuron stably transcribes one out of more than ~2,000 OR alleles1,2. OR gene choice is mediated by a multi-chromosomal enhancer hub that activates transcription at a single OR3,4, followed by ORtranslation dependent feedback that stabilizes this choice5,6. However, with more than one OR enhancer hub in each nucleus7, the mechanism by which only one OR allele is chosen for transcription remains enigmatic. Here, using single cell genomics, we show that only one of the OR enhancer hubs formed in each neuron retains euchromatic features and sustains transcriptional competence. Further, we provide evidence that OR transcription recruits enhancers and reinforces enhancer hub activity locally, while OR RNA inhibits transcription in competing hubs over distance, promoting OR protein-independent transition to singularity. While OR RNA synthesis is sufficient to break the symmetry between equipotent enhancer hubs, OR translation stabilizes transcription at the prevailing hub, revealing dual non-coding and coding mechanisms implemented by OR RNAs for transcriptional prevalence. We propose that coding mRNAs can function as “selfish” non-coding RNAs that influence nuclear architecture, enhance their own transcription, and inhibit their competitors, with generalizable implications in probabilistic cell fate decisions.

2023-09-28 | GSE232194 | GEO

Long non-coding RNAs from divergent transcription of protein-coding genes

Project description:A remarkable number of long non-coding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origins of these molecules in individual cell types is poorly understood. As a prerequisite to studying the transcriptional regulation of lncRNAs, we conducted a comprehensive analysis of the genomic origins of lncRNAs expressed in embryonic stem cells (ESCs).

2012-08-28 | GSE36799 | GEO

The Polycomb Group Gene EMF2B modulates protein coding and non-coding RNAs in developing rice panicles.

Project description:The Polycomb Repressive Complex 2 (PRC2) represses the transcriptional activity of target genes through trimethylation of Lysine 27 of Histone H3. The functions of the plant PRC2 have been chiefly described in Arabidopsis but specific PRC2 functions in other plant species, especially the cereals, are still largely unknown. Here we utilize ChIP-seq data in the analysis of protein coding and non-coding RNAs in early WT panicles of rice.

2018-05-31 | GSE62550 | GEO

Evolved differences in cis and trans regulation between the maternal and zygotic mRNA complements in the Drosophila embryo

Project description:During embryogenesis in animals, initial developmental processes are driven entirely by maternally provided gene products that are deposited into the oocyte. The zygotic genome is transcriptionally activated later, when developmental control is handed off from maternal gene products to the zygote during the maternal to zygotic transition (MZT). The MZT is highly regulated and conserved across all animals, and while some details change across model systems where it has been studied, most are too evolutionarily diverged to make comparisons as to how this process evolves. There are differences in maternal gene products and their zygotic complements across Drosophila species, so here we used hybrid crosses between sister species of Drosophila (D. simulans, D. sechellia, and D. mauritiana) and transcriptomics to determine how gene regulation changes in early embryogenesis across species. We find that regulation of maternal transcript deposition and zygotic transcription evolve through different mechanisms. Changes in transcript levels occur predominantly through differences in trans regulation for maternal genes, while changes in zygotic transcription occur through a combination of regulatory changes in cis, trans, and both cis and trans. We find that patterns of transcript level inheritance in hybrids relative to parental species differs between maternal and zygotic transcripts; maternal transcript levels are more likely to be conserved but both stages have a large proportion of transcripts showing dominance of one parental species. Differences in the underlying regulatory landscape in the mother and the zygote are likely the primary determinants for how maternal and zygotic transcripts evolve species.

2020-11-24 | GSE136646 | GEO

RNA-seq analysis of Mycobacterium avium TMC724 vs. M. avium 104 non-coding and coding transcriptome

Project description:Deep sequencing was implemented to study the transcriptional landscape of Mycobacterium avium TMC724. High-resolution transcriptome analysis identified the transcription start points for 652 genes. One third of these coincided with the start codons and therefore belong to leaderless transcripts, whereas the rest of the transcripts had 5' UTRs with the mean length of 83 nt. In addition, the 5' UTRs of 6 genes contained SAM-IV and Ykok types of riboswitches. 87 antisense RNAs and 9 intergenic small RNAs were mapped. Four of the revealed intergenic small RNAs, including igMAV_1034-1035 expressed at a very high level, have no homologs in M. tuberculosis, whilst M. avium lacks several intergenic sRNAs present in M. tuberculosis. Among those, MTS479 and MTS1338 are of special interest due to their possible implication in pathogenesis. Elucidation of differences in the repertoire of intergenic sRNAs between the two mycobacterial species may improve our understanding of mycobacterial diseases pathogenesis. Transcriptional profile of Mycobacterium avium TMC724, grown at 37M-BM-0C in Dubos broth until mid-logarithmic growth phase

2013-04-23 | E-GEOD-46281 | biostudies-arrayexpress

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