scholarly journals Genomic methods in profiling DNA accessibility and factor localization

2019 ◽  
Vol 28 (1) ◽  
pp. 69-85 ◽  
Author(s):  
David C. Klein ◽  
Sarah J. Hainer
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Regulatory Regions ◽  
Histone Proteins ◽  
Putative Gene ◽  
Factor Binding ◽  
Advantages And Disadvantages ◽  
Dna Accessibility

AbstractRecent advancements in next-generation sequencing technologies and accompanying reductions in cost have led to an explosion of techniques to examine DNA accessibility and protein localization on chromatin genome-wide. Generally, accessible regions of chromatin are permissive for factor binding and are therefore hotspots for regulation of gene expression; conversely, genomic regions that are highly occupied by histone proteins are not permissive for factor binding and are less likely to be active regulatory regions. Identifying regions of differential accessibility can be useful to uncover putative gene regulatory regions, such as enhancers, promoters, and insulators. In addition, DNA-binding proteins, such as transcription factors that preferentially bind certain DNA sequences and histone proteins that form the core of the nucleosome, play essential roles in all DNA-templated processes. Determining the genomic localization of chromatin-bound proteins is therefore essential in determining functional roles, sequence motifs important for factor binding, and regulatory networks controlling gene expression. In this review, we discuss techniques for determining DNA accessibility and nucleosome positioning (DNase-seq, FAIRE-seq, MNase-seq, and ATAC-seq) and techniques for detecting and functionally characterizing chromatin-bound proteins (ChIP-seq, DamID, and CUT&RUN). These methods have been optimized to varying degrees of resolution, specificity, and ease of use. Here, we outline some advantages and disadvantages of these techniques, their general protocols, and a brief discussion of their development. Together, these complimentary approaches have provided an unparalleled view of chromatin architecture and functional gene regulation.

Mammalian genome evolution as a result of epigenetic regulation of transposable elements

2014 ◽  
Vol 5 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Reuben M. Buckley ◽  
David L. Adelson
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Epigenetic Regulation ◽  
Dna Sequences ◽  
Defense Mechanisms ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Epigenetic Marks ◽  
Rna Molecules ◽  
Mammalian Genomes

AbstractTransposable elements (TEs) make up a large proportion of mammalian genomes and are a strong evolutionary force capable of rewiring regulatory networks and causing genome rearrangements. Additionally, there are many eukaryotic epigenetic defense mechanisms able to transcriptionally silence TEs. Furthermore, small RNA molecules that target TE DNA sequences often mediate these epigenetic defense mechanisms. As a result, epigenetic marks associated with TE silencing can be reestablished after epigenetic reprogramming – an event during the mammalian life cycle that results in widespread loss of parental epigenetic marks. Furthermore, targeted epigenetic marks associated with TE silencing may have an impact on nearby gene expression. Therefore, TEs may have driven species evolution via their ability to heritably alter the epigenetic regulation of gene expression in mammals.

Meta-analysis of transcriptome data identified TGTCNN motif variants associated with the response to plant hormone auxin in Arabidopsis thaliana L.

2016 ◽  
Vol 14 (02) ◽  
pp. 1641009 ◽  
Author(s):  
Elena V. Zemlyanskaya ◽  
Daniil S. Wiebe ◽  
Nadezhda A. Omelyanchuk ◽  
Victor G. Levitsky ◽  
Victoria V. Mironova
Keyword(s):  
Gene Expression ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Gene Promoters ◽  
Auxin Response ◽  
Regulatory Regions ◽  
Core Motif ◽  
Functional Roles ◽  
Functional Features ◽  
Time Specific

Auxin is the major regulator of plant growth and development. It regulates gene expression via a family of transcription factors (ARFs) that bind to auxin responsive elements (AuxREs) in the gene promoters. The canonical AuxREs found in regulatory regions of many auxin responsive genes contain the TGTCTC core motif, whereas ARF binding site is a degenerate TGTCNN with TGTCGG strongly preferred. Thereby two questions arise: which TGTCNN variants are functional AuxRE cores and whether different TGTCNN variants have distinct functional roles? In this study, we performed meta-analysis of microarray data to reveal TGTCNN variants essential for auxin response and to characterize their functional features. Our results indicate that four TGTCNN motifs (TGTCTC, TGTCCC, TGTCGG, and TGTCTG) are associated with auxin up-regulation and two (TGTCGG, TGTCAT) with auxin down-regulation, but to a lesser extent. The genes having some of these motifs in their regulatory regions showed time-specific auxin response. Functional annotation of auxin up- and down-regulated genes also revealed GO terms specific for the auxin-regulated genes with certain TGTCNN variants in their promoters. Our results provide an idea that various TGTCNN motifs may play distinct roles in the auxin regulation of gene expression.

scholarly journals Mechanisms and Evolution of Control Logic in Prokaryotic Transcriptional Regulation

2009 ◽  
Vol 73 (3) ◽  
pp. 481-509 ◽  
Author(s):  
Sacha A. F. T. van Hijum ◽  
Marnix H. Medema ◽  
Oscar P. Kuipers
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Control Logic ◽  
Transcriptional Regulatory Networks ◽  
Regulatory Regions ◽  
Evolutionary Origins ◽  
Drive Gene Expression ◽  
Transcriptional Regulatory ◽  
Drive Gene

SUMMARY A major part of organismal complexity and versatility of prokaryotes resides in their ability to fine-tune gene expression to adequately respond to internal and external stimuli. Evolution has been very innovative in creating intricate mechanisms by which different regulatory signals operate and interact at promoters to drive gene expression. The regulation of target gene expression by transcription factors (TFs) is governed by control logic brought about by the interaction of regulators with TF binding sites (TFBSs) in cis-regulatory regions. A factor that in large part determines the strength of the response of a target to a given TF is motif stringency, the extent to which the TFBS fits the optimal TFBS sequence for a given TF. Advances in high-throughput technologies and computational genomics allow reconstruction of transcriptional regulatory networks in silico. To optimize the prediction of transcriptional regulatory networks, i.e., to separate direct regulation from indirect regulation, a thorough understanding of the control logic underlying the regulation of gene expression is required. This review summarizes the state of the art of the elements that determine the functionality of TFBSs by focusing on the molecular biological mechanisms and evolutionary origins of cis-regulatory regions.

scholarly journals Regulatory mechanisms of gene expression: complexity with elements of deterministic chaos.

2006 ◽  
Vol 53 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Jolanta Jura ◽  
Paulina Wegrzyn ◽  
Jacek Jura ◽  
Aleksander Koj
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Linear Models ◽  
Nonlinear Models ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Deterministic Chaos ◽  
Mrna Translation ◽  
Hard Determinism ◽  
Complex Relationships

Linear models based on proportionality between variables have been commonly applied in biology and medicine but in many cases they do not describe correctly the complex relationships of living organisms and now are being replaced by nonlinear theories of deterministic chaos. Recent advances in molecular biology and genome sequencing may lead to a simplistic view that all life processes in a cell, or in the whole organism, are strictly and in a linear fashion controlled by genes. In reality, the existing phenotype arises from a complex interaction of the genome and various environmental factors. Regulation of gene expression in the animal organism occurs at the level of epigenetic DNA modification, RNA transcription, mRNA translation, and many additional alterations of nascent proteins. The process of transcription is highly complicated and includes hundreds of transcription factors, enhancers and silencers, as well as various species of low molecular mass RNAs. In addition, alternative splicing or mRNA editing can generate a family of polypeptides from a single gene. Rearrangement of coding DNA sequences during somatic recombination is the source of great variability in the structure of immunoglobulins and some other proteins. The process of rearrangement of immunoglobulin genes, or such phenomena as parental imprinting of some genes, appear to occur in a random fashion. Therefore, it seems that the mechanism of genetic information flow from DNA to mature proteins does not fit the category of linear relationship based on simple reductionism or hard determinism but would be probably better described by nonlinear models, such as deterministic chaos.

scholarly journals Extended Archaeal Histone-Based Chromatin Structure Regulates Global Gene Expression in Thermococcus kodakarensis

2021 ◽  
Vol 12 ◽  
Author(s):  
Travis J. Sanders ◽  
Fahad Ullah ◽  
Alexandra M. Gehring ◽  
Brett W. Burkhart ◽  
Robert L. Vickerman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Regulation Of Gene Expression ◽  
Model Organism ◽  
Global Gene Expression ◽  
Single Amino Acid ◽  
Post Translational Modification ◽  
Histone Proteins ◽  
Thermococcus Kodakarensis ◽  
Archaeal Histone

Histone proteins compact and organize DNA resulting in a dynamic chromatin architecture impacting DNA accessibility and ultimately gene expression. Eukaryotic chromatin landscapes are structured through histone protein variants, epigenetic marks, the activities of chromatin-remodeling complexes, and post-translational modification of histone proteins. In most Archaea, histone-based chromatin structure is dominated by the helical polymerization of histone proteins wrapping DNA into a repetitive and closely gyred configuration. The formation of the archaeal-histone chromatin-superhelix is a regulatory force of adaptive gene expression and is likely critical for regulation of gene expression in all histone-encoding Archaea. Single amino acid substitutions in archaeal histones that block formation of tightly packed chromatin structures have profound effects on cellular fitness, but the underlying gene expression changes resultant from an altered chromatin landscape have not been resolved. Using the model organism Thermococcus kodakarensis, we genetically alter the chromatin landscape and quantify the resultant changes in gene expression, including unanticipated and significant impacts on provirus transcription. Global transcriptome changes resultant from varying chromatin landscapes reveal the regulatory importance of higher-order histone-based chromatin architectures in regulating archaeal gene expression.

scholarly journals In plants distal regulatory sequences overlap with unmethylated rather than low-methylated regions, in contrast to mammals

2020 ◽  
Author(s):  
Rurika Oka ◽  
Mattijs Bliek ◽  
Huub C.J. Hoefsloot ◽  
Maike Stam
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Transcriptional Repression ◽  
Genome Stability ◽  
Regulation Of Gene Expression ◽  
Regulatory Sequences ◽  
Regulatory Regions ◽  
Plant Genomes ◽  
Underlying Mechanisms

AbstractBackgroundDNA methylation is an important factor in the regulation of gene expression and genome stability. High DNA methylation levels are associated with transcriptional repression. In mammalian systems, unmethylated, low methylated and fully methylated regions (UMRs, LMRs, and FMRs, respectively) can be distinguished. UMRs are associated with proximal regulatory regions, while LMRs are associated with distal regulatory regions. Although DNA methylation is mainly limited to the CG context in mammals, while it occurs in CG, CHG and CHH contexts in plants, UMRs and LMRs were expected to occupy similar genomic sequences in both mammals and plants.ResultsThis study investigated major model and crop plants such as Arabidopsis thaliana, tomato (Solanum lycopersicum), rice (Oryza sativa) and maize (Zea mays), and shows that plant genomes can also be subdivided in UMRs, LMRs and FMRs, but that LMRs are mainly present in the CHG context rather than the CG context. Strikingly, the identified CHG LMRs were enriched in transposable elements rather than regulatory regions. Maize candidate regulatory regions overlapped with UMRs. LMRs were enriched for heterochromatic histone modifications and depleted for DNase accessibility and H3K9 acetylation. CHG LMRs form a distinct, abundant cluster of loci, indicating they have a different role than FMRs.ConclusionsBoth mammalian and plant genomes can be segmented in three distinct classes of loci, UMRs, LMRs and FMRs, indicating similar underlying mechanisms. Unlike in mammals, distal regulatory sequences in plants appear to overlap with UMRs instead of LMRs. Our data indicate that LMRs in plants have a different function than those in mammals.

scholarly journals In Search of Selectivity: Design, Synthesis, and Biological Evaluation of New Classes of HDAC Inhibitors

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 63
Author(s):  
L. M. Viranga Tillekeratne ◽  
Ayad Ayad Al-Hamashi ◽  
Samkeliso Dlamini ◽  
William Taylor ◽  
Radhika Koranne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Sequences ◽  
Metal Binding ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Hdac Inhibitors ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Design And Synthesis ◽  
Epigenetic Modulation

Epigenetic regulation of gene expression without changing DNA sequences is a promising strategy in developing therapeutic agents for human diseases, especially cancer. Histone deacetylases (HDACs) are a family of enzymes involved in epigenetic modulation of gene expression by chromatin remodeling. Deacetylation of the lysine side chains of histones by HDAC proteins renders DNA transcriptionally inactive, resulting in the inhibition of expression of tumor suppressor genes, leading to tumorigenesis and tumor progression. Therefore, inhibiting HDAC enzymes has become an attractive strategy to modulate gene expression as a strategy for developing anticancer drugs. There are currently four FDA-approved cancer drugs in clinical use, and many more are in different stages of clinical trials. However, their clinical utility is limited due to undesirable side effects, mainly attributed to their lack of selectivity and the presence of a hydroxamic acid moiety as the metal-binding group. There are eighteen different isoforms of HDACs belonging to four classes that have been identified in humans. A major challenge in HDAC inhibitor development is how to make them selective for these HDAC isoforms and classes. We report the design and synthesis of new classes of HDAC inhibitors and the evaluation of their anticancer activity and selectivity.

scholarly journals DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters?

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1424 ◽  
Author(s):  
Ordoñez ◽  
Martínez-Calle ◽  
Agirre ◽  
Prosper
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Myeloproliferative Neoplasms ◽  
Regulation Of Gene Expression ◽  
Fine Tuning ◽  
Specific Gene ◽  
Gene Promoters ◽  
Regulatory Regions ◽  
Genome Wide

Gene regulation through DNA methylation is a well described phenomenon that has a prominent role in physiological and pathological cell-states. This epigenetic modification is usually grouped in regions denominated CpG islands, which frequently co-localize with gene promoters, silencing the transcription of those genes. Recent genome-wide DNA methylation studies have challenged this paradigm, demonstrating that DNA methylation of regulatory regions outside promoters is able to influence cell-type specific gene expression programs under physiologic or pathologic conditions. Coupling genome-wide DNA methylation assays with histone mark annotation has allowed for the identification of specific epigenomic changes that affect enhancer regulatory regions, revealing an additional layer of complexity to the epigenetic regulation of gene expression. In this review, we summarize the novel evidence for the molecular and biological regulation of DNA methylation in enhancer regions and the dynamism of these changes contributing to the fine-tuning of gene expression. We also analyze the contribution of enhancer DNA methylation on the expression of relevant genes in acute myeloid leukemia and chronic myeloproliferative neoplasms. The characterization of the aberrant enhancer DNA methylation provides not only a novel pathogenic mechanism for different tumors but also highlights novel potential therapeutic targets for myeloid derived neoplasms.

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