Differences in directionality of RNA polymerase initiation underlie epigenome differences between plants and animals
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ABSTRACT:
PROVIDER: PRJNA638678 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptional regulation is a universal mechanism for a wide array of biological processes, and is driven in large part by genetic enhancer elements. These regulatory elements have been well-studied in animal species, yet their plant counterparts remain poorly characterized. While high-throughput profiling of animal genomes has yielded great success in identifying genetic enhancers through secondary characteristics – flanking histone posttranslational modifications (PTMs), chromatin accessibility, and the production of enhancer RNAs (eRNAs) – it is an active line of investigation as to whether these secondary characteristics can be used in a similar way to locate regulatory regions of plant genomes. Here, we compare the enrichment of the four histone PTMs most commonly associated with animal enhancers – H3K27ac, H3K27me3, H3K4me1, and H3K4me3 – between Drosophila melanogaster, Homo sapiens, and Arabidopsis thaliana genomes. Regions of accessible chromatin were identified through ATAC-seq or DNase-seq, and were analyzed as putative enhancer regions. Additionally, as it has been shown that enhancer activity varies widely from cell type to cell type, matched, single-cell type datasets were used for each species whenever available. Through the intersection of these data it becomes clear that there are distinct differences between the epigenetic makeup of plant and animal genomes. While these four histone PTMs are present at transcription start sites (TSSs) in all three of the species investigated, A. thaliana showed a marked depletion of these modifications upstream of the TSS, while the animal species showed bimodal enrichment. The plant histone PTM pattern is consistent with the pattern observed at unidirectional promoters, which was further supported by GRO-seq data. When intergenic regions of accessible chromatin were examined – putative enhancer regions – the plant epigenomes showed a one-sided, rather than bimodal, enrichment of all four of the histone PTMs. However, these sites retain the ability to produce eRNAs, suggesting that they are likely functionally active enhancer elements. While it is known that animal promoters and enhancers have bidirectional transcription, this analysis revealed that plant promoters and enhancers have a distinct pattern, and only exhibit histone PTM deposition and transcription in the sense direction. While further investigation is merited, this may speak to a fundamental difference between the transcriptional machinery of plant and animal kingdoms.
2020-06-11 | GSE152243 | GEO
Project description:RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient and focused than in the antisense direction. After transcription begins, directionality is maintained by the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9). INTS11 terminates antisense transcription, whereas sense transcription is protected from this attenuation by CDK9. However, INTS11 terminates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 abrogates attenuation by INTS11. Therefore, transcriptional initiation and the asymmetric activities of CDK9 and INTS11 explain the attenuation of antisense transcription, the more extensive nature of sense transcription, and promoter directionality.
2024-03-19 | GSE243265 | GEO
Project description:RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient and focused than in the antisense direction. After transcription begins, directionality is maintained by the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9). INTS11 terminates antisense transcription, whereas sense transcription is protected from this attenuation by CDK9. However, INTS11 terminates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 abrogates attenuation by INTS11. Therefore, transcriptional initiation and the asymmetric activities of CDK9 and INTS11 explain the attenuation of antisense transcription, the more extensive nature of sense transcription, and promoter directionality.
2024-03-19 | GSE243264 | GEO
Project description:RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient and focused than in the antisense direction. After transcription begins, directionality is maintained by the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9). INTS11 terminates antisense transcription, whereas sense transcription is protected from this attenuation by CDK9. However, INTS11 terminates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 abrogates attenuation by INTS11. Therefore, transcriptional initiation and the asymmetric activities of CDK9 and INTS11 explain the attenuation of antisense transcription, the more extensive nature of sense transcription, and promoter directionality.
2024-03-19 | GSE243262 | GEO
Project description:RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient and focused than in the antisense direction. After transcription begins, directionality is maintained by the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9). INTS11 terminates antisense transcription, whereas sense transcription is protected from this attenuation by CDK9. However, INTS11 terminates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 abrogates attenuation by INTS11. Therefore, transcriptional initiation and the asymmetric activities of CDK9 and INTS11 explain the attenuation of antisense transcription, the more extensive nature of sense transcription, and promoter directionality.
2024-03-19 | GSE243260 | GEO
Project description:RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient and focused than in the antisense direction. After transcription begins, directionality is maintained by the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9). INTS11 terminates antisense transcription, whereas sense transcription is protected from this attenuation by CDK9. However, INTS11 terminates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 abrogates attenuation by INTS11. Therefore, transcriptional initiation and the asymmetric activities of CDK9 and INTS11 explain the attenuation of antisense transcription, the more extensive nature of sense transcription, and promoter directionality.
2024-03-19 | GSE243259 | GEO
Project description:Differences in cell cycle status underlie transcriptional heterogeneity in the HSC compartment
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Project description:Transcription of the mammalian genome is pervasive, but productive transcription outside of protein-coding genes is limited by unknown mechanisms. In particular, although RNA polymerase II (RNAPII) initiates divergently from most active gene promoters, productive elongation occurs primarily in the sense-coding direction. Here we show in mouse embryonic stem cells that asymmetric sequence determinants flanking gene transcription start sites control promoter directionality by regulating promoter-proximal cleavage and polyadenylation. We find that upstream antisense RNAs are cleaved and polyadenylated at poly(A) sites (PASs) shortly after initiation. De novo motif analysis shows PAS signals and U1 small nuclear ribonucleoprotein (snRNP) recognition sites to be the most depleted and enriched sequences, respectively, in the sense direction relative to the upstream antisense direction. These U1 snRNP sites and PAS sites are progressively gained and lost, respectively, at the 5' end of coding genes during vertebrate evolution. Functional disruption of U1 snRNP activity results in a dramatic increase in promoter-proximal cleavage events in the sense direction with slight increases in the antisense direction. These data suggest that a U1-PAS axis characterized by low U1 snRNP recognition and a high density of PASs in the upstream antisense region reinforces promoter directionality by promoting early termination in upstream antisense regions, whereas proximal sense PAS signals are suppressed by U1 snRNP. We propose that the U1-PAS axis limits pervasive transcription throughout the genome. 3' end sequencing of poly (A) + RNAs in mouse ES cells with and without U1 snRNP inhibition using antisense morpholino oligonucleotides (AMO). Each with two biological replicates.
2013-06-28 | E-GEOD-46433 | biostudies-arrayexpress
Project description:Clostridioides difficile strain:food animals | isolate:food animals Genome sequencing
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