Divergent Transcription: A Driving Force for New Gene Origination?
ABSTRACT The mammalian genome is extensively transcribed, a large fraction of which is divergent transcription from promoters and enhancers that is tightly coupled with active gene transcription. Here, we propose that divergent transcription may shape the evolution of the genome by new gene origination.
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ABSTRACT: Several post-translational histone modifications are mainly found in gene promoters and are associated with the promoter activity. It has been hypothesized that histone modifications regulate the transcription, as opposed to the traditional view with transcription factors as the key regulators. Promoters of most active genes do not only initiate transcription of the coding sequence, but also a substantial amount of transcription of the antisense strand upstream of the transcription start site (TSS). This promoter feature has generally not been considered in previous studies of histone modifications and transcription factor binding. We annotated protein-coding genes as bi- or unidirectional depending on their mode of transcription and compared histone modifications and transcription factor occurrences between them. We found that H3K4me3, H3K9ac, and H3K27ac were significantly more enriched upstream of the TSS in bidirectional genes compared with the unidirectional ones. In contrast, the downstream histone modification signals were similar, suggesting that the upstream histone modifications might be a consequence of transcription rather than a cause. Notably, we found well-positioned CTCF and RAD21 peaks approximately 60-80 bp upstream of the TSS in the unidirectional genes. The peak heights were related to the amount of antisense transcription and we hypothesized that CTCF and cohesin act as a barrier against antisense transcription. Our results provide insights into the distribution of histone modifications at promoters and suggest a novel role of CTCF and cohesin as regulators of transcriptional direction.BMC Genomics 04/2015; 16(1):300. DOI:10.1186/s12864-015-1485-5 · 4.04 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are endogenous, single-stranded small RNAs that have important regulatory functions at the post-transcriptional level. In the present study, we characterize miRNAs in two divergent mosquito species, Aedes aegypti and Anopheles stephensi, through deep sequencing of small RNAs spanning all developmental stages. We discovered eight novel miRNAs in Ae. aegypti and 20 novel miRNAs in An. stephensi, which enabled the first systematic analysis of miRNA evolution in mosquitos. We traced the phylogenetic history of all miRNAs in both species and report a rate of 0.055–0.13 miRNA net gain per million years. Most novel miRNAs originate de novo. Duplications that produced miRNA clusters and families are more common in Ae. aegypti than in An. stephensi. We also identified arm-switch as a source of new miRNAs. Expression profile analysis identified mosquito-specific miRNAs that showed strong stage-specific expression in one or both lineages. For example, the aae-miR-2941/2946 family represents the most abundant maternally deposited and zygotically transcribed miRNAs in Ae. aegypti. miR-2943 is a highly expressed zygotic miRNA in both Ae. aegypti and An. stephensi. Such information provides the basis from which to study the function of these miRNAs in biology common to all mosquitos or unique to one particular lineage.Insect Molecular Biology 12/2014; 24(2). DOI:10.1111/imb.12152 · 2.98 Impact Factor
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ABSTRACT: Major features of transcription by human RNA polymerase II (Pol II) remain poorly defined due to a lack of quantitative approaches for visualizing Pol II progress at nucleotide resolution. We developed a simple and powerful approach for performing native elongating transcript sequencing (NET-seq) in human cells that globally maps strand-specific Pol II density at nucleotide resolution. NET-seq exposes a mode of antisense transcription that originates downstream and converges on transcription from the canonical promoter. Convergent transcription is associated with a distinctive chromatin configuration and is characteristic of lower-expressed genes. Integration of NET-seq with genomic footprinting data reveals stereotypic Pol II pausing coincident with transcription factor occupancy. Finally, exons retained in mature transcripts display Pol II pausing signatures that differ markedly from skipped exons, indicating an intrinsic capacity for Pol II to recognize exons with different processing fates. Together, human NET-seq exposes the topography and regulatory complexity of human gene expression. Copyright © 2015 Elsevier Inc. All rights reserved.Cell 04/2015; 161(3):541-554. DOI:10.1016/j.cell.2015.03.010 · 33.12 Impact Factor