Purification of mouse MEP-1, a nuclear protein which binds to the metal regulatory elements of genes encoding metallothionein

AbstractChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.

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miRNA proxy approach reveals hidden functions of glycosylation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1502076112 ◽

2015 ◽

Vol 112 (23) ◽

pp. 7327-7332 ◽

Cited By ~ 21

Author(s):

Tomasz Kurcon ◽

Zhongyin Liu ◽

Anika V. Paradkar ◽

Christopher A. Vaiana ◽

Sujeethraj Koppolu ◽

...

Keyword(s):

Posttranslational Modification ◽

Epithelial To Mesenchymal Transition ◽

Biological Function ◽

Regulatory Elements ◽

Rapid Identification ◽

Mesenchymal Transition ◽

Disease States ◽

Mesenchymal To Epithelial Transition ◽

Genes Encoding ◽

Target Network

Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we pinpoint genes encoding multiple promesenchymal glycosylation enzymes (glycogenes). We focus on three enzymes, beta-1,3-glucosyltransferase (B3GLCT), beta-galactoside alpha-2,3-sialyltransferase 5 (ST3GAL5), and (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5), encoding glycans that are difficult to analyze by traditional methods. Silencing these glycogenes phenocopied the effect of miR-200f, inducing mesenchymal-to-epithelial transition. In addition, all three are up-regulated in TGF-β–induced EMT, suggesting tight integration within the EMT-signaling network. Our work indicates that miRNA can act as a relatively simple proxy to decrypt which glycogenes, including those encoding difficult-to-analyze structures (e.g., proteoglycans, glycolipids), are functionally important in a biological pathway, setting the stage for the rapid identification of glycosylation enzymes driving disease states.

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Thebric à braclocus consists of two paralogous genes encoding BTB/POZ domain proteins and acts as a homeotic and morphogenetic regulator of imaginal development inDrosophila

Development ◽

10.1242/dev.129.10.2419 ◽

2002 ◽

Vol 129 (10) ◽

pp. 2419-2433 ◽

Cited By ~ 6

Author(s):

Jean-Louis Couderc ◽

Dorothea Godt ◽

Susan Zollman ◽

Jiong Chen ◽

Michelle Li ◽

...

Keyword(s):

Tissue Distribution ◽

Nuclear Protein ◽

Drosophila Species ◽

Sexually Dimorphic ◽

Conserved Domains ◽

Gene Dose ◽

Highly Sensitive ◽

Genes Encoding ◽

Redundant Functions ◽

Related Morphology

The bric à brac (bab) locus acts as a homeotic and morphogenetic regulator in the development of ovaries, appendages and the abdomen. It consists of two structurally and functionally related genes, bab1 and bab2, each of which encodes a single nuclear protein. Bab1 and Bab2 have two conserved domains in common, a BTB/POZ domain and a Psq domain, a motif that characterizes a subfamily of BTB/POZ domain proteins in Drosophila. The tissue distribution of Bab1 and Bab2 overlaps, with Bab1 being expressed in a subpattern of Bab2. Analysis of a series of mutations indicates that the two bab genes have synergistic, distinct and redundant functions during imaginal development. Interestingly, several reproduction-related traits that are sexually dimorphic or show diversity among Drosophila species are highly sensitive to changes in the bab gene dose, suggesting that alterations in bab activity may contribute to evolutionary modification of sex-related morphology.

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Optimization of Yarrowia lipolytica-based consolidated biocatalyst through synthetic biology approach: transcription units and signal peptides shuffling

10.21203/rs.3.rs-17224/v1 ◽

2020 ◽

Author(s):

Ewelina Celińska ◽

Monika Borkowska ◽

Paulina Korpys-Woźniak ◽

Monika Kubiak ◽

Jean-Marc Nicaud ◽

...

Keyword(s):

Gene Copy Number ◽

Regulatory Elements ◽

Gene Copy ◽

Signal Peptides ◽

Synthetic Dna ◽

Batch Bioreactor ◽

Genes Encoding ◽

Valuable Compounds ◽

Synthetic Biology Approach ◽

Lipids Accumulation

Abstract Background: Nowadays considerable effort is being pursued towards development of consolidated microbial biocatalysts that will be able to utilize complex, non-pretreated substrates and produce valuable compounds. In such engineered microbes, synthesis of extracellular hydrolases may be fine-tuned by different approaches, like strength of promoter, type of secretory tag, gene copy number etc. In this study, we investigated if organization of a multi-element expression cassette impacts the resultant Y. lipolytica transformants’ phenotype, presuming that different variants of the cassette are composed of the same regulatory elements and encode the same hydrolases. Results: To this end, Y. lipolytica cells were transformed with expression cassettes bearing a pair of genes encoding exactly the same mature amylases, but fused to four different signal peptides (SP), and located interchangeably in either first or second position of a synthetic DNA construction. The resultant strains were tested for growth on raw and pre-treated complex substrates of different plant origin for comprehensive examination of the strains’ acquired characteristics. The best strain’s performance was tested in batch bioreactor cultivations for growth and lipids accumulation. Conclusions: Based on the conducted research we concluded that the positional order of transcription units (TU) and the type of exploited SP affect final characteristics of the resultant consolidated biocatalyst strains, and thus could be considered as additional factors to be evaluated upon consolidated biocatalysts optimization.

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Rewiring of the Transcription Factor Network in Acute Myeloid Leukemia

Cancer Informatics ◽

10.1177/1176935119859863 ◽

2019 ◽

Vol 18 ◽

pp. 117693511985986 ◽

Cited By ~ 1

Author(s):

Salam A Assi ◽

Constanze Bonifer ◽

Peter N Cockerill

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Transcription Factors ◽

Myeloid Leukemia ◽

Regulatory Networks ◽

Regulatory Elements ◽

Genes Encoding ◽

Myeloid Development ◽

Mitogen Activated Protein ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous cancer associated with different patterns of gene expression determined by the nature of their DNA mutations. These mutations mostly act to deregulate gene expression by various mechanisms at the level of the nucleus. By performing genome-wide epigenetic profiling of cis-regulatory elements, we found that AML encompasses different mutation-specific subclasses associated with the rewiring of the gene regulatory networks that drive differentiation into different directions away from normal myeloid development. By integrating epigenetic profiles with gene expression and chromatin conformation data, we defined pathways within gene regulation networks that were differentially rewired within each mutation-specific subclass of AML. This analysis revealed 2 major classes of AML: one class defined by mutations in signaling molecules that activate AP-1 via the mitogen-activated protein (MAP) kinase pathway and a second class defined by mutations within genes encoding transcription factors such as RUNX1/CBFβ and C/EBPα. By identifying specific DNA motifs protected from DNase I digestion at cis-regulatory elements, we were able to infer candidate transcription factors bound to these motifs. These integrated analyses allowed the identification of AML subtype-specific core regulatory networks that are required for AML development and maintenance, which could now be targeted in personalized therapies.

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Phytochrome signal-transduction: characterization of pathways and isolation of mutants

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1995.0139 ◽

1995 ◽

Vol 350 (1331) ◽

pp. 67-74 ◽

Cited By ~ 13

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Red Light ◽

Signal Transduction Pathway ◽

Regulatory Elements ◽

Signal Transduction Pathways ◽

Expression Of Genes ◽

Genes Encoding ◽

Regulated Gene Expression ◽

Dependent Pathway

The study of phytochrome signalling has yielded a wealth of data describing both the perception of light by the receptor, and the terminal steps in phytochrome-regulated gene expression by a number of transcription factors. We are now focusing on establishing the intervening steps linking phytochrome photoactivation to gene expression, and the regulation and interactions of these signalling pathways. Recent work has utilized both a pharmacological approach in phototrophic soybean suspension cultures and microinjection techniques in tomato to establish three distinct phytochrome signal-transduction pathways: (i) a calcium-dependent pathway that regulates the expression of genes encoding the chlorophyll a/b binding protein ( CAB ) and other components of photosystem II; (ii) a cGMP-dependent pathway that regulates the expression of the gene encoding chalcone synthase ( CHS ) and the production of anthocyanin pigments; and (iii) a pathway dependent upon both calcium and cGMP that regulates the expression of genes encoding components of photosystem I and is necessary for the production of mature chloroplasts. To study the components and the regulation of phytochrome signal-transduction pathways, mutants with altered photomorphogenic responses have been isolated by a number of laboratories. However, with several possible exceptions, little real progress has been made towards the isolation of mutants in positive regulatory elements of the phytochrome signal-transduction pathway. We have characterized a novel phytochrome A (phyA)-mediated far-red light (FR) response in Arabidopsis seedlings which we are currently using to screen for specific phyA signal-transduction mutants.

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CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts – a bioinformatical analysis

Biological Chemistry ◽

10.1515/bc.2009.124 ◽

2009 ◽

Vol 390 (11) ◽

Cited By ~ 3

Author(s):

Ke Xiao ◽

Franz Jehle ◽

Christoph Peters ◽

Thomas Reinheckel ◽

R. Heiner Schirmer ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Gene Locus ◽

Regulatory Elements ◽

Malaria Parasites ◽

Mrna Regulation ◽

Genome Wide ◽

Bioinformatical Analysis ◽

Genes Encoding ◽

Rna Motif ◽

Medical Interest

Abstract In genome-wide screens we studied CA/C1 peptidases of malaria-causing plasmodia and their hosts (man and mouse). For Plasmodium falciparum and P. berghei, several new CA/C1 peptidase genes encoding proteases of the L- and B-family with specific promoter modules were identified. In addition, two new human CA/C1 peptidase loci and one new mouse gene locus were found; otherwise, the sets of CA/C1 peptidase genes in man and mouse seem to be complete now. In each species studied there is a multitude of CA/C1 peptidases with lysosomal localization signals and partial functional overlap according to similar but subfamily-specific structures. Individual target structures in plasmodia include residues specifically different in CA/C1 peptidase subsite 2. This is of medical interest considering CA/C1 peptidase inhibition for chemotherapy in malaria, malignancies and other diseases. Promoter structures and mRNA regulation differ widely among CA/C1 peptidase subfamilies and between mammals and plasmodia. We characterized promoter modules conserved in mouse and man for the CA/C1 peptidase families B and L (with the L-like subfamily, F-like subfamily and mouse-specific J-like subfamily). RNA motif searches revealed conserved regulatory elements such as GAIT elements; plasmodial CA/C1 peptidase mRNA elements include ARE elements and mammalian mRNAs contain 15-lox DICE elements.

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Nerve-Derived Trophic Factors and DNA Elements Controlling Expression of Genes Encoding Synaptic Proteins in Skeletal Muscle Fibers

Canadian Journal of Applied Physiology ◽

10.1139/h98-021 ◽

1998 ◽

Vol 23 (4) ◽

pp. 366-376 ◽

Cited By ~ 2

Author(s):

Bernard J. Jasmin ◽

Anthony O. Gramolini ◽

Feisal A. Adatia ◽

Lindsay Angus ◽

Céline Boudreau-Larivière ◽

...

Keyword(s):

Neuromuscular Junction ◽

Transcriptional Activation ◽

Recombinant Dna ◽

Signal Transduction Pathway ◽

Regulatory Elements ◽

Postsynaptic Membrane ◽

Synaptic Proteins ◽

Trophic Factors ◽

Recombinant Dna Technology ◽

Genes Encoding

The neuromuscular junction represents an excellent model system for studying various critical issues in neurobiology at the molecular, cellular, and physiological levels. Our understanding of the basic events underlying synpase formation, maintenance, and plasticity has progressed considerably over the last few years primarily because of the numerous studies that have focused on this synapse and used sophisticated recombinant DNA technology. Recent data indicate that myonuclei located in the vicinity of the postsynaptic membrane are in a differential state of transcription compared to nuclei of the extrasynaptic sarcoplasm. Thus, renewal of postsynaptic membrane proteins appears to occur via a mechanism involving the local transcriptional activation of genes encoding these specialized proteins and extracellular cues originating from motoneurons. Such interaction between presynaptic nerve terminals and the postsynaptic sarcoplasm indicates that the entire signal transduction pathway is compartmentalized at the level of the neuromuscular junction. Expression of these genes appears less coregulated than originally anticipated, indicating that maintenance of the postsynaptic membrane requires the contribution of multiple extracellular signals, which ultimately urge target transcription factors to distinct DNA regulatory elements via various second messenger systems. Key words: neuromuscular junction, synapse, acetylcholinesterase, utrophin, agrin, CGRP, promoter, mRNA

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Phloem fibres as motors of gravitropic behaviour of flax plants: level of transcriptome

Functional Plant Biology ◽

10.1071/fp16348 ◽

2018 ◽

Vol 45 (2) ◽

pp. 203 ◽

Cited By ~ 6

Author(s):

Oleg Gorshkov ◽

Natalia Mokshina ◽

Nadezda Ibragimova ◽

Marina Ageeva ◽

Natalia Gogoleva ◽

...

Keyword(s):

Cell Wall ◽

Large Scale ◽

Turgor Pressure ◽

Control Plant ◽

Transcriptome Profiling ◽

Transcript Abundance ◽

Regulatory Elements ◽

Wall Structure ◽

Vertical Position ◽

Genes Encoding

Restoration of stem vertical position after plant inclination is a widely spread version of plant orientation in accordance with gravity vector direction. Gravitropic behaviour of flax plants involves the formation of curvature in stem region that has ceased elongation long in advance of stem inclination. The important participants of such behaviour are phloem fibres with constitutively formed tertiary cell wall (G-layer). We performed the large-scale transcriptome profiling of phloem fibres isolated from pulling and opposite sides of gravitropic curvature and compared with control plant fibres. Significant changes in transcript abundance take place for genes encoding proteins of several ion channels, transcription factors and other regulating elements. The largest number of upregulated genes belonged to the cell wall category; many of those were specifically upregulated in fibres of pulling stem side. The obtained data permit to suggest the mechanism of fibre participation in gravitropic reaction that involves the increase of turgor pressure and the rearrangements of cell wall structure in order to improve contractile properties, and to identify the regulatory elements that operate specifically in the fibres of the pulling stem side making gelatinous phloem fibres an important element of gravitropic response in herbaceous plants.

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Chlamydial Type III Secretion System Is Encoded on Ten Operons Preceded by Sigma 70-Like Promoter Elements

Journal of Bacteriology ◽

10.1128/jb.01034-06 ◽

2006 ◽

Vol 189 (1) ◽

pp. 198-206 ◽

Cited By ~ 48

Author(s):

P. Scott Hefty ◽

Richard S. Stephens

Keyword(s):

Type Iii Secretion ◽

Transcriptional Start Site ◽

Type Iii Secretion System ◽

Regulatory Elements ◽

Secretion System ◽

Secretion Systems ◽

Promoter Elements ◽

Type Iii ◽

Type Iii Secretion Systems ◽

Genes Encoding

ABSTRACT Many gram-negative bacterial pathogens employ type III secretion systems for infectious processes. Chlamydiae are obligate intracellular bacteria that encode a conserved type III secretion system that is likely requisite for growth. Typically, genes encoding type III secretion systems are located in a single locus; however, for chlamydiae these genes are scattered throughout the genome. Little is known regarding the gene regulatory mechanisms for this essential virulence determinant. To facilitate identification of cis-acting transcriptional regulatory elements, the operon structure was determined. This analysis revealed 10 operons that contained 37 genes associated with the type III secretion system. Linkage within these operons suggests a role in type III secretion for each of these genes, including 13 genes encoding proteins with unknown function. The transcriptional start site for each operon was determined. In conjunction with promoter activity assays, this analysis revealed that the type III secretion system operons encode σ70-like promoter elements. Transcriptional initiation by a sigma factor responsible for constitutive gene expression indicates that undefined activators or repressors regulate developmental stage-specific expression of chlamydial type III secretion system genes.

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