scholarly journals Combinatorial Gene Regulatory Functions Underlie Ultraconserved Elements in Drosophila

2016 ◽  
Vol 33 (9) ◽  
pp. 2294-2306 ◽  
Author(s):  
Maria Warnefors ◽  
Britta Hartmann ◽  
Stefan Thomsen ◽  
Claudio R. Alonso
Keyword(s):  
Ultraconserved Elements ◽  
Gene Regulatory ◽  
Regulatory Functions

scholarly journals Exosomic microRNAs as emerging key regulators of intercellular communication in the tumor microenvironment and beyond

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Mariam Murtadha ◽  
Muller Fabbri
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Intercellular Communication ◽  
Potential Role ◽  
Biological Fluids ◽  
Healthy Controls ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Regulatory Functions

AbstractMicroRNAs (miRs) are small non-coding RNAs with key gene regulatory functions. Recent evidence has shown that miRs have a central role in shaping the biology of the Tumor Microenvironment (TME). The discovery that some exosomes contain high levels of miR cargo that shuttle between cells and mediate intercellular cross-talk has shifted the focus of miR research towards understanding the biological role of exosomic miRs. In this review, we highlight the emerging role of exosomic miRs in molding the tumor microenvironment towards pro-tumor conditions by altering intercellular communication. We briefly discuss some mechanisms of selective loading of miRs into exosomes, as well as emerging evidence that exosomic miRs are present in all biological fluids. Furthermore, we describe the differences in the exosomic miR signatures between cancer patients and healthy controls, and the potential role of exosomic miRs as diagnostic, prognostic, and therapeutic biomarkers.

scholarly journals Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive Chlamydia trachomatis Biovars

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Michael John Patton ◽  
Chih-Yu Chen ◽  
Chunfu Yang ◽  
Stuart McCorrister ◽  
Chris Grant ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Virulence Factor ◽  
Chlamydial Infection ◽  
Virulence Genes ◽  
Negative Regulation ◽  
Host Protein ◽  
Regulatory Function ◽  
Important Virulence Factor ◽  
Gene Regulatory ◽  
Regulatory Functions

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease.C. trachomatisisolates are classified into 2 biovars—lymphogranuloma venereum (LGV) and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. TheC. trachomatisplasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-curedC. trachomatisserovars A and D (trachoma biovar), a L2 serovar (LGV biovar), and the L2 serovar transformed with a plasmid containing a nonsense mutation inpgp4to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within bothC. trachomatisbiovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF) for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature.IMPORTANCETheChlamydia trachomatisplasmid is an important virulence factor in the pathogenesis of chlamydial infection. It is known that plasmid protein 4 (Pgp4) functions in the transcriptional regulation of the plasmid virulence protein 3 (Pgp3) and multiple chromosomal loci of unknown function. Since many gene regulatory functions can be post-transcriptional, we undertook a comparative proteomic analysis to better understand the plasmid’s role in chlamydial and host protein expression. We report that Pgp4 is a potent and specific master positive regulator of a common core of plasmid and chromosomal virulence genes shared by multipleC. trachomatisserovars. Notably, we show that the plasmid is a negative regulator of the expression of the chlamydial virulence factor CPAF. The plasmid regulation of CPAF is independent of Pgp4 and restricted to aC. trachomatismacrophage-tropic strain. These findings are important because they define a previously unknown role for the plasmid in the pathophysiology of invasive chlamydial infection.

scholarly journals Allosteric Mechanism of the V. vulnificus Adenine Riboswitch Resolved by Four-dimensional Chemical Mapping

2017 ◽  
Author(s):  
Siqi Tian ◽  
Wipapat Kladwang ◽  
Rhiju Das
Keyword(s):  
Strong Support ◽  
Chemical Mapping ◽  
Rna Molecules ◽  
Conformational Selection ◽  
Allosteric Mechanism ◽  
Ligand Free ◽  
Gene Regulatory ◽  
Nucleotide Resolution ◽  
Regulatory Functions ◽  
Structural Heterogeneities

ABSTRACTThe structural interconversions that mediate the gene regulatory functions of RNA molecules may be different from classic models of allostery, but the relevant structural correlations have remained elusive in even intensively studied systems. Here, we present a four-dimensional expansion of chemical mapping called lock-mutate-map-rescue (LM2R), which integrates multiple layers of mutation with nucleotide-resolution chemical mapping. This technique resolves the core mechanism of the adenine-responsive V. vulnificus add riboswitch, a paradigmatic system for which both Monod-Wyman-Changeux (MWC) conformational selection models and non-MWC alternatives have been proposed. To discriminate amongst these models, we locked each functionally important helix through designed mutations and assessed formation or depletion of other helices via compensatory rescue evaluated by chemical mapping. These LM2R measurements give strong support to the pre-existing correlations predicted by MWC models, disfavor alternative models, and suggest additional structural heterogeneities that may be general across ligand-free riboswitches.

An analysis of the class of gene regulatory functions implied by a biochemical model

Biosystems ◽  
2006 ◽  
Vol 84 (2) ◽  
pp. 81-90 ◽  
Author(s):  
John Grefenstette ◽  
Sohyoung Kim ◽  
Stuart Kauffman
Keyword(s):  
Biochemical Model ◽  
Gene Regulatory ◽  
Regulatory Functions

scholarly journals The gene regulatory system for specifying germ layers in early embryos of the simple chordate

2021 ◽  
Vol 7 (24) ◽  
pp. eabf8210
Author(s):  
Miki Tokuoka ◽  
Kazuki Maeda ◽  
Kenji Kobayashi ◽  
Atsushi Mochizuki ◽  
Yutaka Satou
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Regulatory Genes ◽  
Cell Stage ◽  
Germ Layers ◽  
Early Embryos ◽  
Gene Expression Dynamics ◽  
Gene Regulatory ◽  
Regulatory Functions

In animal embryos, gene regulatory networks control the dynamics of gene expression in cells and coordinate such dynamics among cells. In ascidian embryos, gene expression dynamics have been dissected at the single-cell resolution. Here, we revealed mathematical functions that represent the regulatory logics of all regulatory genes expressed at the 32-cell stage when the germ layers are largely specified. These functions collectively explain the entire mechanism by which gene expression dynamics are controlled coordinately in early embryos. We found that regulatory functions for genes expressed in each of the specific lineages contain a common core regulatory mechanism. Last, we showed that the expression of the regulatory genes became reproducible by calculation and controllable by experimental manipulations. Thus, these regulatory functions represent an architectural design for the germ layer specification of this chordate and provide a platform for simulations and experiments to understand the operating principles of gene regulatory networks.

scholarly journals SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis

Science ◽  
2018 ◽  
Vol 360 (6390) ◽  
pp. 800-805 ◽  
Author(s):  
Matthias Muhar ◽  
Anja Ebert ◽  
Tobias Neumann ◽  
Christian Umkehrer ◽  
Julian Jude ◽  
...  
Keyword(s):  
Direct Gene ◽  
Gene Regulatory ◽  
Regulatory Functions

scholarly journals Mechanism of Gene Regulation by a Staphylococcus aureus Toxin

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Hwang-Soo Joo ◽  
Som S. Chatterjee ◽  
Amer E. Villaruz ◽  
Seth W. Dickey ◽  
Vee Y. Tan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Gene Regulation ◽  
Toxin Production ◽  
Bacterial Toxin ◽  
Human Pathogen ◽  
Bacterial Physiology ◽  
Functional Specification ◽  
Gene Regulatory ◽  
Regulatory Functions

ABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus , depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production. IMPORTANCE Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection.

scholarly journals Tissue-Specific Regulation of Translational Readthrough Tunes Functions of the Traffic Jam Transcription Factor

2020 ◽  
Author(s):  
Prajwal Karki ◽  
Travis D. Carney ◽  
Cristina Maracci ◽  
Andriy S. Yatsenko ◽  
Halyna R. Shcherbata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Neural Cells ◽  
Tissue Specific ◽  
Traffic Jam ◽  
Translational Readthrough ◽  
The Central Nervous System ◽  
Gene Regulatory ◽  
Specific Regulation ◽  
Regulatory Functions

SummaryTranslational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR is pervasive in eukaryotic organisms; however, its biological significance remains unclear. In this study, we quantify the TR potential of several candidate genes in Drosophila melanogaster and characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). We used CRISPR/Cas9 generated mutant flies to show that the TR-generated Tj isoform is expressed in the nuclei of a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads, which express the short Tj isoform only. Translational control of TR is critical for preservation of neuronal integrity and maintenance of reproductive health. Fine-tuning of the gene regulatory functions of transcription factors by TR provides a new potential mechanism for cell-specific regulation of gene expression.HighlightsTj undergoes tissue-specific TR in neural cells of the central nervous system.Strict control of TR is crucial for neuroprotection and maintenance of reproductive capacity.TR selectively fine-tunes the gene regulatory functions of the transcription factor.TR in Tj links transcription and translation of tissue-specific control of gene expression.

scholarly journals Quantitative single cell 5hmC sequencing reveals non-canonical gene regulation by non-CG hydroxymethylation

2021 ◽  
Author(s):  
Emily B. Fabyanic ◽  
Peng Hu ◽  
Qi Qiu ◽  
Kiara N. Berrios ◽  
Jennifer Flournoy ◽  
...  
Keyword(s):  
Single Cell ◽  
Bisulfite Sequencing ◽  
Single Cells ◽  
Oxidative Modification ◽  
Biological Processes ◽  
Single Nucleus ◽  
Cell Type Specific ◽  
Gene Regulatory ◽  
Regulatory Functions

Oxidative modification of 5-methylcytosine (5mC) generates 5-hydroxymethylcytosine (5hmC), a DNA modification that exhibits unique epigenetic regulatory functions and impacts diverse biological processes. However, standard single-nucleus/cell bisulfite sequencing methods cannot resolve the base ambiguity between 5mC and 5hmC to accurately measure cell-type specific epigenomic patterns and gene regulatory functions of 5hmC or true 5mC. Here, we develop single-nucleus 5hmC sequencing (snhmC-seq) for quantitative and unbiased 5hmC profiling in single cells by harnessing differential deaminase activity of APOBEC3A towards 5mC and chemically protected 5hmC. We used snhmC-seq to profile single nuclei from cryopreserved mouse brain samples to reveal epigenetic heterogeneity of 5hmC at single-cell resolution and uncovered a non-canonical gene regulatory role of genic 5hmC in non-CG context.

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