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Nature Aug 2021Deciphering the principles and mechanisms by which gene activity orchestrates complex cellular arrangements in multicellular organisms has far-reaching implications for... (Review)
Review
Deciphering the principles and mechanisms by which gene activity orchestrates complex cellular arrangements in multicellular organisms has far-reaching implications for research in the life sciences. Recent technological advances in next-generation sequencing- and imaging-based approaches have established the power of spatial transcriptomics to measure expression levels of all or most genes systematically throughout tissue space, and have been adopted to generate biological insights in neuroscience, development and plant biology as well as to investigate a range of disease contexts, including cancer. Similar to datasets made possible by genomic sequencing and population health surveys, the large-scale atlases generated by this technology lend themselves to exploratory data analysis for hypothesis generation. Here we review spatial transcriptomic technologies and describe the repertoire of operations available for paths of analysis of the resulting data. Spatial transcriptomics can also be deployed for hypothesis testing using experimental designs that compare time points or conditions-including genetic or environmental perturbations. Finally, spatial transcriptomic data are naturally amenable to integration with other data modalities, providing an expandable framework for insight into tissue organization.
Topics: Animals; Data Analysis; Disease; Gene Expression Profiling; Humans; Organ Specificity; Transcription, Genetic; Transcriptome
PubMed: 34381231
DOI: 10.1038/s41586-021-03634-9 -
Nature Reviews. Molecular Cell Biology Oct 2018RNA polymerase II (Pol II) core promoters are specialized DNA sequences at transcription start sites of protein-coding and non-coding genes that support the assembly of... (Review)
Review
RNA polymerase II (Pol II) core promoters are specialized DNA sequences at transcription start sites of protein-coding and non-coding genes that support the assembly of the transcription machinery and transcription initiation. They enable the highly regulated transcription of genes by selectively integrating regulatory cues from distal enhancers and their associated regulatory proteins. In this Review, we discuss the defining properties of gene core promoters, including their sequence features, chromatin architecture and transcription initiation patterns. We provide an overview of molecular mechanisms underlying the function and regulation of core promoters and their emerging functional diversity, which defines distinct transcription programmes. On the basis of the established properties of gene core promoters, we discuss transcription start sites within enhancers and integrate recent results obtained from dedicated functional assays to propose a functional model of transcription initiation. This model can explain the nature and function of transcription initiation at gene starts and at enhancers and can explain the different roles of core promoters, of Pol II and its associated factors and of the activating cues provided by enhancers and the transcription factors and cofactors they recruit.
Topics: Animals; Chromatin; DNA; Eukaryota; Gene Expression Regulation; Humans; Promoter Regions, Genetic; RNA Polymerase II; Transcription Factors; Transcription Initiation, Genetic; Transcription, Genetic
PubMed: 29946135
DOI: 10.1038/s41580-018-0028-8 -
Biochimica Et Biophysica Acta Jan 2013A minimal RNA polymerase II (pol II) transcription system comprises the polymerase and five general transcription factors (GTFs) TFIIB, -D, -E, -F, and -H. The addition... (Review)
Review
A minimal RNA polymerase II (pol II) transcription system comprises the polymerase and five general transcription factors (GTFs) TFIIB, -D, -E, -F, and -H. The addition of Mediator enables a response to regulatory factors. The GTFs are required for promoter recognition and the initiation of transcription. Following initiation, pol II alone is capable of RNA transcript elongation and of proofreading. Structural studies reviewed here reveal roles of GTFs in the initiation process and shed light on the transcription elongation mechanism. This article is part of a Special Issue entitled: RNA Polymerase II Transcript Elongation.
Topics: Amino Acid Sequence; Animals; Humans; Models, Biological; Models, Molecular; Molecular Sequence Data; RNA Polymerase II; Sequence Homology, Amino Acid; Structure-Activity Relationship; Transcription Factors, General; Transcription, Genetic
PubMed: 23000482
DOI: 10.1016/j.bbagrm.2012.09.003 -
Neuron Oct 2018Gene transcription is the process by which the genetic codes of organisms are read and interpreted as a set of instructions for cells to divide, differentiate, migrate,... (Review)
Review
Gene transcription is the process by which the genetic codes of organisms are read and interpreted as a set of instructions for cells to divide, differentiate, migrate, and mature. As cells function in their respective niches, transcription further allows mature cells to interact dynamically with their external environment while reliably retaining fundamental information about past experiences. In this Review, we provide an overview of the field of activity-dependent transcription in the vertebrate brain and highlight contemporary work that ranges from studies of activity-dependent chromatin modifications to plasticity mechanisms underlying adaptive behaviors. We identify key gaps in knowledge and propose integrated approaches toward a deeper understanding of how activity-dependent transcription promotes the refinement and plasticity of neural circuits for cognitive function.
Topics: Animals; Behavior; Brain; Cognition; Humans; Neuronal Plasticity; Neurons; Transcription, Genetic
PubMed: 30359600
DOI: 10.1016/j.neuron.2018.10.013 -
Molecular Cell Aug 2018Many mechanisms contribute to regulation of gene expression to ensure coordinated cellular behaviors and fate decisions. Transcriptional responses to external signals... (Review)
Review
Many mechanisms contribute to regulation of gene expression to ensure coordinated cellular behaviors and fate decisions. Transcriptional responses to external signals can consist of many hundreds of genes that can be parsed into different categories based on kinetics of induction, cell-type and signal specificity, and duration of the response. Here we discuss the structure of transcription programs and suggest a basic framework to categorize gene expression programs based on characteristics related to their control mechanisms. We also discuss possible evolutionary implications of this framework.
Topics: Animals; Gene Expression Regulation; Humans; Organ Specificity; Signal Transduction; Transcription Factors; Transcription, Genetic; Transcriptome
PubMed: 30075140
DOI: 10.1016/j.molcel.2018.07.017 -
Transcription Oct 2020Increasingly sophisticated biochemical and genetic techniques are unraveling the regulatory factors and mechanisms that control gene expression in the Archaea. While... (Review)
Review
Increasingly sophisticated biochemical and genetic techniques are unraveling the regulatory factors and mechanisms that control gene expression in the Archaea. While some similarities in regulatory strategies are universal, archaeal-specific regulatory strategies are emerging to complement a complex patchwork of shared archaeal-bacterial and archaeal-eukaryotic regulatory mechanisms employed in the archaeal domain. The prokaryotic archaea encode core transcription components with homology to the eukaryotic transcription apparatus and also share a simplified eukaryotic-like initiation mechanism, but also deploy tactics common to bacterial systems to regulate promoter usage and influence elongation-termination decisions. We review the recently established complete archaeal transcription cycle, highlight recent findings of the archaeal transcription community and detail the expanding post-initiation regulation imposed on archaeal transcription.
Topics: Archaea; Transcription, Genetic
PubMed: 33112729
DOI: 10.1080/21541264.2020.1838865 -
Cell Jan 2019Transcriptional regulation in metazoans occurs through long-range genomic contacts between enhancers and promoters, and most genes are transcribed in episodic "bursts"...
Transcriptional regulation in metazoans occurs through long-range genomic contacts between enhancers and promoters, and most genes are transcribed in episodic "bursts" of RNA synthesis. To understand the relationship between these two phenomena and the dynamic regulation of genes in response to upstream signals, we describe the use of live-cell RNA imaging coupled with Hi-C measurements and dissect the endogenous regulation of the estrogen-responsive TFF1 gene. Although TFF1 is highly induced, we observe short active periods and variable inactive periods ranging from minutes to days. The heterogeneity in inactive times gives rise to the widely observed "noise" in human gene expression and explains the distribution of protein levels in human tissue. We derive a mathematical model of regulation that relates transcription, chromosome structure, and the cell's ability to sense changes in estrogen and predicts that hypervariability is largely dynamic and does not reflect a stable biological state.
Topics: Estrogen Receptor alpha; Estrogens; Gene Expression; Gene Expression Regulation; Humans; Models, Theoretical; Promoter Regions, Genetic; RNA, Messenger; Single-Cell Analysis; Transcription, Genetic; Transcriptional Activation; Trefoil Factor-1
PubMed: 30554876
DOI: 10.1016/j.cell.2018.11.026 -
Biochimica Et Biophysica Acta.... Jan 2019Transcription termination by the RNA polymerase (RNAP) is a fundamental step of gene expression that involves the release of the nascent transcript and dissociation of... (Review)
Review
Transcription termination by the RNA polymerase (RNAP) is a fundamental step of gene expression that involves the release of the nascent transcript and dissociation of the RNAP from the DNA template. However, the functional importance of termination extends beyond the mere definition of the gene borders. Chloroplasts originate from cyanobacteria and possess their own gene expression system. Plastids have a unique hybrid transcription system consisting of two different types of RNAPs of dissimilar phylogenetic origin together with several additional nuclear encoded components. Although the basic components involved in chloroplast transcription have been identified, little attention has been paid to the chloroplast transcription termination. Recent identification and functional characterization of novel factors in regulating transcription termination in Arabidopsis chloroplasts via genetic and biochemical approaches have provided insights into the mechanisms and significance of transcription termination in chloroplast gene expression. This review provides an overview of the current knowledge of the transcription termination in chloroplasts.
Topics: Arabidopsis; Chloroplasts; Transcription Termination, Genetic; Transcription, Genetic
PubMed: 30414934
DOI: 10.1016/j.bbabio.2018.11.011 -
Transcription 2020
Topics: Adaptation, Physiological; Plants; Transcription, Genetic
PubMed: 33252015
DOI: 10.1080/21541264.2020.1837498 -
Nucleus (Austin, Tex.) Jan 2018Numerous studies based on new single-cell and single-gene techniques show that individual genes can be transcribed in short bursts or pulses accompanied by changes in... (Review)
Review
Numerous studies based on new single-cell and single-gene techniques show that individual genes can be transcribed in short bursts or pulses accompanied by changes in pulsing frequencies. Since so many examples of such discontinuous or fluctuating transcription have been found from prokaryotes to mammals, it now seems to be a common mode of gene expression. In this review we discuss the occurrence of the transcriptional fluctuations, the techniques used for their detection, their putative causes, kinetic characteristics, and probable physiological significance.
Topics: Animals; Humans; Kinetics; Transcription, Genetic
PubMed: 29285985
DOI: 10.1080/19491034.2017.1419112