Promoter Structures Conserved between Homo Sapiens, Mus Musculus and Drosophila Melanogaster

Author(s):  
Boris R. Jankovic ◽  
John A. C. Archer ◽  
Rajesh Chowdhary ◽  
Ulf Schaefer ◽  
Vladimir B. Bajic

Some of the key processes in living organisms remain essentially unchanged even in evolutionarily very distant species. Transcriptional regulation is one such fundamental process that is essential for cell survival. Transcriptional control exerts great part of its effects at the level of transcription initiation mediated through protein-DNA interactions mainly at promoters but also at other control regions. In this chapter, the authors identify conserved families of motifs of promoter regulatory structures between Homo sapiens, Mus musculus and Drosophila melanogaster. By a promoter regulatory structure they consider here a combination of motifs from identified motif families. Conservation of promoter structure across these vertebrate and invertebrate genomes suggests the presence of a fundamental promoter architecture and provides the basis for deeper understanding of the necessary components of the transcription regulation machinery. The authors reveal the existence of families of DNA sequence motifs that are shared across all three species in upstream promoter regions. They further analyze the relevance of our findings for better understanding of preserved regulatory mechanisms and associated biology insights.

2013 ◽  
pp. 1522-1534
Author(s):  
Boris R. Jankovic ◽  
John A. C. Archer ◽  
Rajesh Chowdhary ◽  
Ulf Schaefer ◽  
Vladimir B. Bajic

Some of the key processes in living organisms remain essentially unchanged even in evolutionarily very distant species. Transcriptional regulation is one such fundamental process that is essential for cell survival. Transcriptional control exerts great part of its effects at the level of transcription initiation mediated through protein-DNA interactions mainly at promoters but also at other control regions. In this chapter, the authors identify conserved families of motifs of promoter regulatory structures between Homo sapiens, Mus musculus and Drosophila melanogaster. By a promoter regulatory structure they consider here a combination of motifs from identified motif families. Conservation of promoter structure across these vertebrate and invertebrate genomes suggests the presence of a fundamental promoter architecture and provides the basis for deeper understanding of the necessary components of the transcription regulation machinery. The authors reveal the existence of families of DNA sequence motifs that are shared across all three species in upstream promoter regions. They further analyze the relevance of our findings for better understanding of preserved regulatory mechanisms and associated biology insights.


2016 ◽  
Author(s):  
Αναστάσιος Αλεξιάδης

Η RNA εξωνουκλεάση ERI-1 (Enhanced RNAi-1) εντοπίστηκε σε μια γενετική σάρωση στο Ceanorabditis elegans σαν αρνητικός ρυθμιστής της RNA παρεμβολής (RNAi). Ο μηχανισμός δράσης που προτάθηκε είναι η αποκοπή των δυο προεξεχόντων νουκλεοτιδίων από τα μικρά παρεμβαλλόμενα RNA (siRNA) γεγονός που τα καθιστά ανενεργά. Το ομόλογό της στον Homo sapiens και στον Mus musculus αλληλεπιδρά με το 3 ́άκρο των ιστονικών μεταγράφων απομακρύνοντας τα τελευταία νουκλεοτίδια τους και συμμετέχοντας στη ρύθμιση της αποικοδόμησης τους στο τέλος της S φάσης. Επιπλέον η ERI-1 στο Schizosaccharomyces pombe, το Ceanorabditis elegans και το Mus musculus συμμετέχει στην ωρίμανση του 5.8S rRNA αποκόπτοντας δυο νουκλεοτίδια από το 3 ́άκρο του. Φαίνεται λοιπόν ότι πρόκειται για μια σημαντική εξωνουκλεάση που παρεμβαίνει σε κεντρικούς κυτταρικούς μηχανισμούς που μεσολαβούνται από μόρια RNA. Για τον λόγο αυτό επιλέξαμε να μελετήσουμε τη δράση της στη Drosophila melanogaster όπου οι γνώσεις μας περιοριζόταν στον βιοχημικό χαρακτηρισμό του εκεί ομολόγου Snipper (Snp) σαν εξωνουκλεάση. Η μελέτη βασίστηκε σε μεταλλάγματα ένθεσης και υποέκφρασης του Snp μέσω RNA παρεμβολής, καθώς και σε διαγονιδιακές σειρές που το υπερεκφράζουν ώστε να διερευνηθεί η πιθανή εμπλοκή του σε κάποιο από τα γνωστά μονοπάτια. Τα αποτελέσματά μας έδειξαν ότι το Snp είναι ένα απαραίτητο γονίδιο για την ανάπτυξη της Drosophila melanogaster. Τα μετάγραφα του παρέχονται στο έμβρυο από την μητέρα και η μείωση της έκφρασης του οδηγεί σε αναστολή της ανάπτυξης σε συγκεκριμένα στάδια. Επιπλέον η υποέκφραση του σε διάφορους ιστούς προκαλεί παραμορφώσεις και αποκλίσεις από τη φυσιολογική τους μορφολογία. Σε συμφωνία με την αποκλίνουσα βιογένεση του 5.8S rRNA στη δροσόφιλα η απουσία του Snp δε φαίνεται να το επηρεάζει. Αντίθετα στην περίπτωση των μεταγράφων των ιστονικών RNA η απουσία του Snp οδηγεί σε ανάλογη μείωση των επιπέδων τους. Το φαινόμενο αυτό οφείλεται σε άμεση επίδραση της πρωτεΐνης Snp επί των ιστονικών mRNA όπως δείξαμε με πειράματα ανοσοκατακρήμνισης. Επιπλέον η αλληλούχιση των 3 ́άκρων των μεταγράφων της ιστόνης 3 έδειξε ότι η επεξεργασία τους απουσία της Snp είναι προβληματική, καθώς δεν αποκόπτονται τα δύο τελικά νουκλεοτίδια. Η υπόθεση πουΑΝΑΣΤΑΣΙΟΣ ΑΛΕΞΙΑΔΗΣ1προτείνεται είναι ότι η Snp συμμετέχει στην ωρίμανση ή/και στην προστασία του 3 ́άκρου των ιστονών. Η απουσία της οδηγεί σε μειωμένη αφθονία των ιστονικών μεταγράφων πιθανότατα λόγω αυξημένης αποικοδόμησης. Αυτό με τη σειρά του καθυστερεί ή αναστέλλει την ολοκλήρωση του κυτταρικού κύκλου.


2013 ◽  
Vol 11 (06) ◽  
pp. 1343001 ◽  
Author(s):  
VENKATA RAJESH YELLA ◽  
MANJU BANSAL

Gene expression is the most fundamental biological process, which is essential for phenotypic variation. It is regulated by various external (environment and evolution) and internal (genetic) factors. The level of gene expression depends on promoter architecture, along with other external factors. Presence of sequence motifs, such as transcription factor binding sites (TFBSs) and TATA-box, or DNA methylation in vertebrates has been implicated in the regulation of expression of some genes in eukaryotes, but a large number of genes lack these sequences. On the other hand, several experimental and computational studies have shown that promoter sequences possess some special structural properties, such as low stability, less bendability, low nucleosome occupancy, and more curvature, which are prevalent across all organisms. These structural features may play role in transcription initiation and regulation of gene expression. We have studied the relationship between the structural features of promoter DNA, promoter directionality and gene expression variability in S. cerevisiae. This relationship has been analyzed for seven different measures of gene expression variability, along with two different regulatory effect measures. We find that a few of the variability measures of gene expression are linked to DNA structural properties, nucleosome occupancy, TATA-box presence, and bidirectionality of promoter regions. Interestingly, gene responsiveness is most intimately correlated with DNA structural features and promoter architecture.


1993 ◽  
Vol 296 (3) ◽  
pp. 663-670 ◽  
Author(s):  
M F Wilkemeyer ◽  
E R Andrews ◽  
F D Ledley

Methylmalonyl-CoA mutase (MCM) is a nuclear-encoded mitochondrial matrix enzyme. We have reported characterization of murine MCM and cloning of a murine MCM cDNA and now describe the murine Mut locus, its promoter and evidence for tissue-specific variation in MCM mRNA, enzyme and holo-enzyme levels. The Mut locus spans 30 kb and contains 13 exons constituting a unique transcription unit. A B1 repeat element was found in the 3′ untranslated region (exon 13). The transcription initiation site was identified and upstream sequences were shown to direct expression of a reporter gene in cultured cells. The promoter contains sequence motifs characteristic of: (1) TATA-less housekeeping promoters; (2) enhancer elements purportedly involved in co-ordinating expression of nuclear-encoded mitochondrial proteins; and (3) regulatory elements including CCAAT boxes, cyclic AMP-response elements and potential AP-2-binding sites. Northern blots demonstrate a greater than 10-fold variation in steady-state mRNA levels, which correlate with tissue levels of enzyme activity. However, the ratio of holoenzyme to total enzyme varies among different tissues, and there is no correlation between steady-state mRNA levels and holoenzyme activity. These results suggest that, although there may be regulation of MCM activity at the level of mRNA, the significance of genetic regulation is unclear owning to the presence of epigenetic regulation of holoenzyme formation.


1990 ◽  
Vol 10 (7) ◽  
pp. 3415-3420
Author(s):  
M W Van Dyke ◽  
M Sawadogo

The existence of separable functions within the human class II general transcription factor TFIID was probed for differential sensitivity to mild proteolytic treatment. Independent of whether TFIID was bound to DNA or free in solution, partial digestion with either one of a variety of nonspecific endoproteases generated a protease-resistant protein product that retained specific DNA recognition, as revealed by DNase I footprinting. However, in contrast to native TFIID, which interacts with the adenovirus major late (ML) promoter over a very broad DNA region, partially proteolyzed TFIID interacted with only a small region of the ML promoter immediately surrounding the TATA sequence. This novel footprint was very similar to that observed with the TATA factor purified from yeast cells. Partially proteolyzed human TFIID could form stable complexes that were resistant to challenge by exogenous templates. It could also nucleate the assembly of transcription complexes on the ML promoter with an efficiency comparable to that of native TFIID, yielding similar levels of transcription initiation. These results suggest a model in which the human TFIID protein is composed of at least two different regions or polypeptides: a protease-resistant "core," which by itself is sufficient for promoter recognition and basal transcriptional levels, and a protease-sensitive "tail," which interacts with downstream promoter regions and may be involved in regulatory processes.


Author(s):  
Oladoja AWofisayo

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols. Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Comments of reviewer(s): Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITORS


2019 ◽  
Vol 14 (5) ◽  
pp. 432-445 ◽  
Author(s):  
Muniba Faiza ◽  
Khushnuma Tanveer ◽  
Saman Fatihi ◽  
Yonghua Wang ◽  
Khalid Raza

Background: MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression at the post-transcriptional level through complementary base pairing with the target mRNA, leading to mRNA degradation and blocking translation process. Many dysfunctions of these small regulatory molecules have been linked to the development and progression of several diseases. Therefore, it is necessary to reliably predict potential miRNA targets. Objective: A large number of computational prediction tools have been developed which provide a faster way to find putative miRNA targets, but at the same time, their results are often inconsistent. Hence, finding a reliable, functional miRNA target is still a challenging task. Also, each tool is equipped with different algorithms, and it is difficult for the biologists to know which tool is the best choice for their study. Methods: We analyzed eleven miRNA target predictors on Drosophila melanogaster and Homo sapiens by applying significant empirical methods to evaluate and assess their accuracy and performance using experimentally validated high confident mature miRNAs and their targets. In addition, this paper also describes miRNA target prediction algorithms, and discusses common features of frequently used target prediction tools. Results: The results show that MicroT, microRNA and CoMir are the best performing tool on Drosopihla melanogaster; while TargetScan and miRmap perform well for Homo sapiens. The predicted results of each tool were combined in order to improve the performance in both the datasets, but any significant improvement is not observed in terms of true positives. Conclusion: The currently available miRNA target prediction tools greatly suffer from a large number of false positives. Therefore, computational prediction of significant targets with high statistical confidence is still an open challenge.


Microbiology ◽  
2005 ◽  
Vol 151 (1) ◽  
pp. 259-268 ◽  
Author(s):  
Birgit Baumgarth ◽  
Frank Wilco Bartels ◽  
Dario Anselmetti ◽  
Anke Becker ◽  
Robert Ros

The exopolysaccharide galactoglucan promotes the establishment of symbiosis between the nitrogen-fixing Gram-negative soil bacterium Sinorhizobium meliloti 2011 and its host plant alfalfa. The transcriptional regulator ExpG activates expression of galactoglucan biosynthesis genes by direct binding to the expA1, expG/expD1 and expE1 promoter regions. ExpG is a member of the MarR family of regulatory proteins. Analysis of target sequences of an ExpG(His)6 fusion protein in the exp promoter regions resulted in the identification of a binding site composed of a conserved palindromic region and two associated sequence motifs. Association and dissociation kinetics of the specific binding of ExpG(His)6 to this binding site were characterized by standard biochemical methods and by single-molecule spectroscopy based on the atomic force microscope (AFM). Dynamic force spectroscopy indicated a distinct difference in the kinetics between the wild-type binding sequence and two mutated binding sites, leading to a closer understanding of the ExpG–DNA interaction.


2017 ◽  
Author(s):  
Sarah Rennie ◽  
Maria Dalby ◽  
Marta Lloret-Llinares ◽  
Stylianos Bakoulis ◽  
Christian Dalager Vaagensø ◽  
...  

ABSTRACTMammalian gene promoters and enhancers share many properties. They are composed of a unified promoter architecture of divergent transcripton initiation and gene promoters may exhibit enhancer function. However, it is currently unclear how expression strength of a regulatory element relates to its enhancer strength and if the unifying architecture is conserved across Metazoa. Here we investigate the transcription initiation landscape and its associated RNA decay in D. melanogaster. Surprisingly, we find that the majority of active gene-distal enhancers and a considerable fraction of gene promoters are divergently transcribed. We observe quantitative relationships between enhancer potential, expression level and core promoter strength, providing an explanation for indirectly related histone modifications that are reflecting expression levels. Lowly abundant unstable RNAs initiated from weak core promoters are key characteristics of gene-distal developmental enhancers, while the housekeeping enhancer strengths of gene promoters reflect their expression strengths. The different layers of regulation mediated by gene-distal enhancers and gene promoters are also reflected in chromatin interaction data. Our results suggest a unified promoter architecture of many D. melanogaster regulatory elements, that is universal across Metazoa, whose regulatory functions seem to be related to their core promoter elements.


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