Significant Role In Gene Regulation Research Articles

Development and characterization of non-coding RNA-derived simple sequence repeat markers in coconut (Cocos nucifera L.).

Non-coding RNA (ncRNA)-based SSR markers are highly useful in molecular breeding as ncRNAs play a significant role in gene regulation. In the present study, for the first time in coconut, we have identified 597 ncRNA-derived SSR markers, including 509 long non-coding RNASSRs (lncRNASSRs) and 88 micro RNASSRs (miRNASSRs). Of these, 20 primers (10 each from lncRNA-SSR and miRNA-SSR) were selected, screened on 6 coconut accessions, and 50% produced polymorphic fragments. These 10 polymorphic primers were used for genotyping 96 palms of 16 coconut accessions, comprising eight tall and dwarf accessions each. The number of alleles ranged from 2 to 9 per SSR marker, with an average of 4.6 alleles per locus. The average heterozygosity and Shannon index were 0.5 and 1.1, respectively, suggesting that ncRNA-SSRs show high polymorphism level. Distance-based cluster analyses revealed that all the tall and dwarf accessions were differentiated and grouped in different clusters. The study demonstrates the usefulness of ncRNA-based SSR markers for assessing genetic diversity and genetic improvement in coconut.

Thermodynamics-based modeling reveals regulatory effects of indirect transcription factor-DNA binding

SummaryTranscription factors (TFs) influence gene expression by binding to DNA, yet experimental data suggests that they also frequently bind regulatory DNA indirectly by interacting with other DNA-bound proteins. Here, we used a data modeling approach to test if such indirect binding by TFs plays a significant role in gene regulation. We first incorporated regulatory function of indirectly bound TFs into a thermodynamics-based model for predicting enhancer-driven expression from its sequence. We then fit the new model to a rich data set comprising hundreds of enhancers and their regulatory activities during mesoderm specification in Drosophila embryogenesis and showed that the newly incorporated mechanism results in significantly better agreement with data. In the process, we derived the first sequence-level model of this extensively characterized regulatory program. We further showed that allowing indirect binding of a TF explains its localization at enhancers more accurately than with direct binding only. Our model also provided a simple explanation of how a TF may switch between activating and repressive roles depending on context.

Differential Expression of Long Non-Coding RNAs and Their Role in Rodent Neuropathic Pain Models.

Neuropathic pain, which is accompanied by an unpleasant sensation, affects the patient’s quality of life severely. Considering the complexity of the neuropathic pain, there are huge unmet medical needs for it while current effective therapeutics remain far from satisfactory. Accordingly, exploration of mechanisms of neuropathic pain could provide new therapeutic insights. While numerous researches have pointed out the contribution of sensory neuron-immune cell interactions, other mechanisms of action, such as long non-coding RNAs (lncRNAs), also could contribute to the neuropathic pain observed in vivo. LncRNAs have more than 200 nucleotides and were originally considered as transcriptional byproducts. However, recent studies have suggested that lncRNAs played a significant role in gene regulation and disease pathogenesis. A substantial number of long non-coding RNAs were expressed differentially in neuropathic pain models. Besides, therapies targeting specific lncRNAs can significantly ameliorate the development of neuropathic pain, which reveals the contribution of lncRNAs in the generation and maintenance of neuropathic pain and provides a new therapeutic strategy. The primary purpose of this review is to introduce recent studies of lncRNAs on different neuropathic pain models.

Improving Chromatin-Interaction Prediction Using Single-Cell Open-Chromatin Profiles and Making Insight Into the Cis-Regulatory Landscape of the Human Brain.

Single-cell open-chromatin profiles have the potential to reveal the pattern of chromatin-interaction in a cell type. However, currently available cis-regulatory network prediction methods using single-cell open-chromatin profiles focus more on local chromatin interactions despite the fact that long-range interactions among genomic sites play a significant role in gene regulation. Here, we propose a method that predicts both short and long-range interactions among genomic sites using single-cell open chromatin profiles. Our method, termed as single-cell epigenome based chromatin-interaction analysis (scEChIA) exploits signal imputation and refined L1 regularization. For a few single-cell open-chromatin profiles, scEChIA outperformed other tools even in terms of accuracy of prediction. Using scEChIA, we predicted almost 0.7 million interactions among genomic sites across seven cell types in the human brain. Further analysis revealed cell type for connection between genes and expression quantitative trait locus (eQTL) in the human brain and making insight about target genes of human-accelerated-elements and disease-associated mutations. Our analysis enabled by scEChIA also hints about the possible action of a few transcription factors (TFs), especially through long-range interaction in brain endothelial cells.

GATA2 Mutation in Twins with Transient Aplastic Anemia after Chloramphenicol Exposure; A Follow up to Nagao and Mauer 1969

A case of identical twins who developed transient aplastic anemia after chloramphenicol exposure was reported by Nagao and Mauer in the New England Journal of Medicine in 1969. Bone marrow (BM) morphology and tritiated thymidine labeling indices were suggestive of a failure of delivery cells from the undifferentiated stem cell compartment. They concluded that an underlying genetic factor which predisposed to the development of drug induced aplastic anemia was highly likely. We now report long term follow up on the twins from that article and have identified that they both harbour a mutation in GATA2. Twin 1 presented with severe pancytopenia at age 8 months, 3 months after chloramphenicol exposure. His leukocytes and erythrocytes had normalized with supportive care, but platelet count (PC) remained low at 92,000/mm3. Later in life, he was diagnosed with transfusion acquired hepatitis C, treated with Sofosbuvir/Velpatasvir. He did not develop recurrent infections, warts, lymphedema, or pulmonary symptoms. At age 51, he was referred to Hematology for asymptomatic thrombocytopenia with a PC of 17,000/mm3. BM aspirate and biopsy showed a variably cellular marrow with relative erythroid hyperplasia and megaloblastoid features. Cytogenetics, FISH for myelodysplastic syndrome (MDS) related abnormalities and a 33 gene panel for MDS/chronic myelomonocytic leukemia related mutations by next generation sequencing were all normal. A next generation sequencing panel of 59 genes associated with hereditary BM failure syndromes was remarkable only for a previously unreported heterozygous mutation in GATA2 (c1040C>A, pThr347Asn). Twin 2 was also exposed to chloramphenicol at 5 months of age and was found to be pancytopenic when evaluated for BM donation for his brother. His pancytopenia spontaneously resolved at the end of observation. Subsequent medical problems included partial complex seizures, dysautonomia, vertigo, chronic pain syndrome and recurrent Clostridium difficile colitis. He had no history of other recurrent infections, warts, lymphedema, or pulmonary symptoms. He had mild asymptomatic cytopenias noted with a white blood cell count of 3600/mm3, a hemoglobin of 12.9 g/dl and a PC of 97,000/mm3 at the age of 50 years. At the age of 52, he was referred to hematology and was asymptomatic with a normal hemogram. DNA sequencing confirmed an identical GATA2 mutation. GATA2, a DNA binding transcription factor with two zinc finger domains, plays a significant role in gene regulation, cell fate decisions and maintenance of the hematopoietic stem cell pool. Excessive GATA2 activity is reported to prevent stem cells from leaving the pool, while insufficient GATA2 activity causes stem cells to differentiate at increased rates thereby depleting the pool. Homozygous GATA deletions/mutations are lethal. Reported mutations include deletions, frame shift mutations, nonsense mutations and point mutations. Many point mutations appear to act by causing haplo-insufficiency. The point mutation in these patients maps in proximity to the C-zinc finger domain and could potentially disrupt an exonic splicing enhancer causing an in-frame deletion of exon six. Clinical syndromes associated with GATA2 mutations include familial BM failure and cytopenia; familial myelodysplastic syndromes and acute myeloid leukemia; immunodeficiency with monocytopenia and recurrent viral, fungal and mycobacterial infections; immunodeficiency with decreased natural killer, dendritic, B cells, and monocytes; Emberger syndrome presenting with myelodysplastic syndrome, warts and lymphedema; and pulmonary alveolar proteinosis. Cytopenia has been the only clinically obvious manifestation in these twins. Chloramphenicol has been associated with two forms of hematological toxicity. The first is a dose related reversible bone marrow suppression presenting as anemia, and the second is idiosyncratic, often fatal, aplastic anemia. It was proposed that these may be opposite ends of a spectrum with an underlying genetic predisposition leading to the more severe forms. The finding of a GATA2 mutation in these patients supports Nagao and Maurer's speculation that an underlying genetic factor affecting stem cell regulation predisposed to the development of chloramphenicol induced aplastic anemia in these twins. Figure Disclosures No relevant conflicts of interest to declare.

Enforced Activation of Enhancer RNAs In Situ through the dCas9 Synergistic Activation Mediator System.

Enhancers are pivotal genomic elements scattered through the mammalian genome and dictate tissue-specific gene expression programs. Increasing evidence has shown that enhancers not only provide DNA binding motifs for transcription factors (TFs) but also generate non-coding RNAs that are referred to as eRNAs. Studies have demonstrated that eRNA transcripts can play significant roles in gene regulation in both physiology and disease. Commonly used methods to investigate the function of eRNAs are constrained to "loss-of-function" approaches by knockdown of eRNAs, or by chemical inhibition of the enhancer transcription. There has not been a robust method to conduct "gain-of-function" studies of eRNAs to mimic specific disease conditions such as human cancer, where eRNAs are often overexpressed. Here, we introduce a method for precisely and robustly activating eRNAs for functional interrogation of their roles by applying the dCas9 mediated Synergistic Activation Mediators (SAM) system. We present the entire workflow of eRNA activation, from the selection of eRNAs, the design of gRNAs to the validation of eRNA activation by RT-qPCR. This method represents a unique approach to study the roles of a particular eRNA in gene regulation and disease development. In addition, this system can be employed for unbiased CRISPR screening to identify phenotype-driving eRNA targets in the context of a specific disease.

Rapid purification method for human SFPQ by implementing zinc-induced polymerization

Splicing factor proline- and glutamine-rich (SFPQ) is an RNA-binding protein, playing significant roles in gene regulation and subnuclear body formation. Our recent serendipitous discovery showed that SFPQ binds zinc directly and forms an infinite polymer that is induced by zinc binding to the protein. The zinc-induced reversible polymerization has led us to exploit this property to develop a rapid purification strategy for SFPQ without the use of affinity tags. In combination with the variation of ionic strength for salting-out of SFPQ, the reversible zinc-induced precipitation of SFPQ reduced the purification time required to obtain pure SFPQ to a single day. The purified protein was subjected to the previously reported crystallization condition. The resulting crystals diffracted to 2.22 Å resolution, confirming the quality of SFPQ purified with this new rapid purification strategy.

Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells.

Transposable elements (TEs) are thought to have helped establish gene regulatory networks. Both the embryonic and extraembryonic lineages of the early mouse embryo have seemingly co-opted TEs as enhancers, but there is little evidence that they play significant roles in gene regulation. Here we tested a set of long terminal repeat TE families for roles as enhancers in mouse embryonic and trophoblast stem cells. Epigenomic and transcriptomic data suggested that a large number of TEs helped to establish tissue-specific gene expression programmes. Genetic editing of individual TEs confirmed a subset of these regulatory relationships. However, a wider survey via CRISPR interference of RLTR13D6 elements in embryonic stem cells revealed that only a minority play significant roles in gene regulation. Our results suggest that a subset of TEs are important for gene regulation in early mouse development, and highlight the importance of functional experiments when evaluating gene regulatory roles of TEs.

Correlation Patterns Between DNA Methylation and Gene Expression in The Cancer Genome Atlas.

Background:DNA methylation is a form of epigenetic modification that has been shown to play a significant role in gene regulation. In cancer, DNA methylation plays an important role by regulating the expression of oncogenes. The role of DNA methylation in the onset and progression of various cancer types is now being elucidated as more large-scale data become available. The Cancer Genome Atlas (TCGA) provides a wealth of information for the analysis of various molecular aspects of cancer genetics. Gene expression data and DNA methylation data from TCGA have been used for a variety of studies. A traditional understanding of the effects of DNA methylation on gene expression has linked methylation of CpG sites in the gene promoter region with the decrease in gene expression. Recent studies have begun to expand this traditional role of DNA methylation.Results:Here we present a pan-cancer analysis of correlation patterns between CpG methylation and gene expression. Using matching patient data from TCGA, 33 cancer-specific correlations were calculated for each CpG site and the expression level of its corresponding gene. These correlations were used to identify patterns on a per-site basis as well as patterns of methylation across the gene body. Using these identified patterns, we found genes that contain conflicting methylation signals beyond the commonly accepted association between the promoter region methylation and silencing of gene expression. Beyond gene body methylation in whole, we examined individual CpG sites and show that, even in the same gene body, some sites can have a contradictory effect on gene expression in cancers.Conclusions:We observed that within promoter regions there was a substantial amount of positive correlation between methylation and gene expression, which contradicts the commonly accepted association. We observed that the correlation between CpG methylation and gene expression does not exhibit in a tissue-specific manner, suggesting that the effects of methylation on gene expression are largely tissue independent. The analysis of correlation associated with the location of the CpG site in the gene body has led to the identification of several different methylation patterns that affect gene expression, and several examples of methylation activating gene expression were observed. Distinctly opposing or conflicting effects were seen in close proximity on the gene body, where negative and positive correlations were seen at the neighboring CpG sites.

Microarray expression profile of long non-coding RNAs in human lung adenocarcinoma.

BackgroundLong non‐coding RNAs (lncRNAs) participate in many biological dynamics and play significant roles in gene regulation. LncRNA expression is altered in many cancers; however, the expressions and functions of lncRNA genes in lung adenocarcinoma (LAD) remain unknown.MethodsLncRNA and messenger RNA (mRNA) expression in LAD without lymphatic metastasis versus paired adjacent non‐tumor (ANT) lung tissues and LAD with versus without lymphatic metastasis were analyzed using Human LncRNA Arraystar V3.0. The expression levels of four downregulated and four upregulated lncRNAs were verified using quantitative real‐time PCR in cells and tissue specimens.ResultsIn this study, 949 lncRNAs and 681 mRNAs had differential expression in LAD without lymphatic metastasis compared to ANT lung tissues, while 2740 lncRNAs and 1714 mRNAs were differentially expressed in LAD with lymphatic metastasis compared to LAD without lymphatic metastasis. The expression patterns of selected lncRNAs (LINC00113, AC005009.1, ARHGAP22‐IT1, AC009411.1, SRGAP3‐AS2, EGFEM1P, FAM66E, and HLA‐F‐AS1) were consistent with microarray data. Differentially expressed mRNA genes were enriched in crucial Gene Ontology terms and pathways.ConclusionOur results revealed differentially expressed lncRNAs in LAD, suggesting lncRNAs may be potential indicators for LAD diagnosis and therapy.

DNA-Templated Silver Nanoclusters for DNA Methylation Detection.

DNA methylation entails the covalent addition of a methyl group to C-5 position of cytosine by a family of DNA methyltransferase enzymes and has a significant role in gene regulation. Epigenetic changes such as DNA methylation of CpG islands located in the promoter region of some tumor suppressor genes are very common in human diseases such as cancer. Detection of aberrant methylation pattern could serve as an excellent diagnostic approach. It is key to develop methods for the direct and simple detection of methylated DNA or of methyltransferase activity without using antibodies, chemical modification, labeling and enzymatic treatments. In this study, we employ DNA-templated silver nanoclusters for detection of DNA methylation. This method entails use of cytosine rich DNA sequence as an effective template. By monitoring changes in fluorescence intensity, DNA methylation and DNA methyltransferase activity is detected. Upon DNA methylation, the fluorescence intensity of DNA templated Ag/NCs is decreased in a linear range when the concentration of methylated DNA is increased.

Integration of DNA Methylation Data and Gene Expression Data for Prostate Adenocarcinoma: A Proof of Concept

Background: Epigenetics is gaining rapid recognition as it accounts for heritable changes that do not involve changes in the coding sequence, but influences change in gene expressions. DNA methylation is the most extensively studied epigenetic mechanism and has been observed to play a significant role in gene regulation and silencing process. Objective: In our present work, we focused on understanding the relationship between DNA methylation and gene expression. As a proof of concept, Prostate Adenocarcinoma (PRAD), the second leading cause of death in men, was extensively studied to unravel the epigenetic abnormalities associated with disease pathogenesis which may contribute to better diagnosis and prevention of prostate cancer. Method: DNA methylation data (level 1) and Gene expression data (level 3) was taken from The Cancer Genome Atlas (TCGA). A total of 36 samples comprising of 18 normal samples and 18 tumor samples were collected from a batch of 184 and matched with tumor samples and normal samples, respectively. The differentially methylated regions were identified and statistical analysis was carried out for the gene expression data amongst the normal and tumor samples. Further, functional enrichment analysis and pathway analysis were carried out for the filtered genes. Results: Our analysis indicated 453 differentially methylated regions with p-value < 0.05, FDR (false discovery rate) value < 0.05 and beta value (methylation) > 0.2. The integration of gene expression data with methylation data resulted in 180 significant correlations from which 112 genes were filtered under stringent conditions. Out of these 112 genes, 74 genes were filtered through visual inspection of results and their functional enrichment analysis resulted in total 27 clusters with a maximum enrichment score of ~1.86. Conclusion: The genes "GSTP1" and "FGFR2" were present in our prioritized filtered significant correlations, and it was discovered that these genes were known to play a primary role in prostate cancer pathway and progression. Therefore, this approach may help to prioritize other novel genes and suggest their involvement in the prostate cancer pathway Keywords: Epigenetics, DNA methylation, Prostate Adenocarcinoma (PRAD), The Cancer Genome Atlas (TCGA), differentially methylated regions, gene Expression.

Ubiquitin-proteasome-dependent degradation of TBP-like protein is prevented by direct binding of TFIIA.

Although the majority of gene expression is driven by TATA-binding protein (TBP)-based transcription machinery, it has been reported that TBP-related factors (TRFs) are also involved in the regulation of gene expression. TBP-like protein (TLP), which is one of the TRFs and exhibits the highest affinity to TFIIA among known proteins, has recently been showed to have significant roles in gene regulation. However, how the level of TLP is maintained invivo has remained unknown. In this study, we explored the mechanism by which TLP protein is turned over invivo and the factor that maintains the amount of TLP. We showed that TLP is rapidly degraded by the ubiquitin-proteasome system and that tight interaction with TFIIA results in protection of TLP from ubiquitin-proteasome-dependent degradation. The half-life of TLP was shown to be less than a few hours, and the proteasome inhibitor MG132 specifically suppressed TLP degradation. Moreover, knockdown and over-expression experiments showed that TFIIA is engaged in stabilization of TLPinvivo. Thus, we showed a novel characteristic of TLP, that is, interaction with TFIIA is essential to suppress proteasome-dependent turnover of TLP, providing a further insight into TLP-governed gene regulation.

YamiPred: A Novel Evolutionary Method for Predicting Pre-miRNAs and Selecting Relevant Features.

MicroRNAs (miRNAs) are small non-coding RNAs, which play a significant role in gene regulation. Predicting miRNA genes is a challenging bioinformatics problem and existing experimental and computational methods fail to deal with it effectively. We developed YamiPred, an embedded classification method that combines the efficiency and robustness of support vector machines (SVM) with genetic algorithms (GA) for feature selection and parameters optimization. YamiPred was tested in a new and realistic human dataset and was compared with state-of-the-art computational intelligence approaches and the prevalent SVM-based tools for miRNA prediction. Experimental results indicate that YamiPred outperforms existing approaches in terms of accuracy and of geometric mean of sensitivity and specificity. The embedded feature selection component selects a compact feature subset that contributes to the performance optimization. Further experimentation with this minimal feature subset has achieved very high classification performance and revealed the minimum number of samples required for developing a robust predictor. YamiPred also confirmed the important role of commonly used features such as entropy and enthalpy, and uncovered the significance of newly introduced features, such as %A-U aggregate nucleotide frequency and positional entropy. The best model trained on human data has successfully predicted pre-miRNAs to other organisms including the category of viruses.

Secondary structural entropy in RNA switch (Riboswitch) identification.

BackgroundRNA regulatory elements play a significant role in gene regulation. Riboswitches, a widespread group of regulatory RNAs, are vital components of many bacterial genomes. These regulatory elements generally function by forming a ligand-induced alternative fold that controls access to ribosome binding sites or other regulatory sites in RNA. Riboswitch-mediated mechanisms are ubiquitous across bacterial genomes. A typical class of riboswitch has its own unique structural and biological complexity, making de novo riboswitch identification a formidable task. Traditionally, riboswitches have been identified through comparative genomics based on sequence and structural homology. The limitations of structural-homology-based approaches, coupled with the assumption that there is a great diversity of undiscovered riboswitches, suggests the need for alternative methods for riboswitch identification, possibly based on features intrinsic to their structure. As of yet, no such reliable method has been proposed.ResultsWe used structural entropy of riboswitch sequences as a measure of their secondary structural dynamics. Entropy values of a diverse set of riboswitches were compared to that of their mutants, their dinucleotide shuffles, and their reverse complement sequences under different stochastic context-free grammar folding models. Significance of our results was evaluated by comparison to other approaches, such as the base-pairing entropy and energy landscapes dynamics. Classifiers based on structural entropy optimized via sequence and structural features were devised as riboswitch identifiers and tested on Bacillus subtilis, Escherichia coli, and Synechococcus elongatus as an exploration of structural entropy based approaches. The unusually long untranslated region of the cotH in Bacillus subtilis, as well as upstream regions of certain genes, such as the sucC genes were associated with significant structural entropy values in genome-wide examinations.ConclusionsVarious tests show that there is in fact a relationship between higher structural entropy and the potential for the RNA sequence to have alternative structures, within the limitations of our methodology. This relationship, though modest, is consistent across various tests. Understanding the behavior of structural entropy as a fairly new feature for RNA conformational dynamics, however, may require extensive exploratory investigation both across RNA sequences and folding models.

A non-parametric peak calling algorithm for DamID-Seq.

Protein—DNA interactions play a significant role in gene regulation and expression. In order to identify transcription factor binding sites (TFBS) of double sex (DSX)—an important transcription factor in sex determination, we applied the DNA adenine methylation identification (DamID) technology to the fat body tissue of Drosophila, followed by deep sequencing (DamID-Seq). One feature of DamID-Seq data is that induced adenine methylation signals are not assured to be symmetrically distributed at TFBS, which renders the existing peak calling algorithms for ChIP-Seq, including SPP and MACS, inappropriate for DamID-Seq data. This challenged us to develop a new algorithm for peak calling. A challenge in peaking calling based on sequence data is estimating the averaged behavior of background signals. We applied a bootstrap resampling method to short sequence reads in the control (Dam only). After data quality check and mapping reads to a reference genome, the peaking calling procedure compromises the following steps: 1) reads resampling; 2) reads scaling (normalization) and computing signal-to-noise fold changes; 3) filtering; 4) Calling peaks based on a statistically significant threshold. This is a non-parametric method for peak calling (NPPC). We also used irreproducible discovery rate (IDR) analysis, as well as ChIP-Seq data to compare the peaks called by the NPPC. We identified approximately 6,000 peaks for DSX, which point to 1,225 genes related to the fat body tissue difference between female and male Drosophila. Statistical evidence from IDR analysis indicated that these peaks are reproducible across biological replicates. In addition, these peaks are comparable to those identified by use of ChIP-Seq on S2 cells, in terms of peak number, location, and peaks width.

Detection of differentially expressed growth dependent noncoding RNAs in Sulfolobus solfataricus

Noncoding RNA mediated gene regulation exists in all the three kingdoms of life including prokaryotes, eukaryotes and archaea. In prokaryotes, the ncRNAs typically bind to the 5’ end of the messenger RNAs to facilitate its activation or repression. The repression of gene expression in eukaryotes by ncRNAs is regulated by its binding to the 3’-untranslated region. A significant amount of information is available on the ncRNA mediated gene regulation in eukaryotes and prokaryotes. However, the data on ncRNA interference mechanisms in archaea are largely based on bioinformatics predictions. More than 300 noncoding RNAs have been bioinformatically predicted to exist in the hyperthemophilic archeon Sulfolobus solfataricus. The main objective of this study was to ascertain the growth dependent differential expression of certain ncRNAs in S. solfataricus. The northern blot analysis confirms that certain ncRNAs are differentially expressed at particular phases of growth while others are constitutively expressed in all phases of growth. One of the three ncRNAs, RNA 22 was expressed constitutively whereas the other two ncRNAs, RNA 43 and RNA 115 was expressed at specific points of growth. In addition, we also attempt to predict the putative mRNAs that are targeted by specific ncRNAs. In conclusion, our study states that in term with the constitutive expression of ncRNAs 22, the predicted targets include a drug resistance transporter and transposase protein which should be down regulated during the normal growth of Sulfolobus. The second candidate, ncRNA 43 was specifically expressed at the late log phase with putative targets that includes critical metabolic proteins. The third RNA analyzed was ncRNA 115. The expression of ncRNA 115 was at the mid-log phase with the predicted target being the Translation recovery factor (TRF). These predictions with functional classifications of the mRNAs relevant in specific growth points out that ncRNAs plays significant role in gene regulation in S. solfataricus. Key words: Noncoding RNA, Sulfolobus, Archaea, gene regulation.

Target Binding Hotspot Secrets of mir1 microRNA in Oryza sativa by using Bioinformatics Approaches

Thermodynamic properties and nucleic acid symmetry of upstream nucleotide regions to the binding sites, insertion sites or upstream to the gene regions in the eukaryotic genomes are very significant in revealing the properties of various elements such as microRNA sequence, gene sequence and Promoter sequence etc. They set signals for various microRNA to bind at specific location in the genomes and these sequences also help in gene regulation with microRNA. The miR-1 microRNA is one of the most important and common type of small microRNA precursor that regulates its target protein's expression in the cell of both plants and animals therefore its study is very significant. The main emphasis of this research and whole idea behind this kind of work is to find out upstream sequences which carry hidden properties like Railway signals and track sign board which can alert the drivers that how the way is ahead. MicroRNAs are of approximately 21-nucleotides long and play very significant role in gene regulation in variety of genes of different organisms. MicroRNAs and mRNAs (messenger RNA) constitute an important part of gene regulatory networks, influencing diverse biological phenomena. The mRNA (messengerRNA) translated in to protein by the process of translation but when microRNA binds to specific mRNA sequence it alters the gene regulation process this results the alteration in the resulting protein and its function. The binding mechanism of microRNA at target site is not very clear so the study in this field may reveal some secrets which can be helpful to understand the process of binding of microRNA at different mRNA for regulation in different genes. The analysis of upstream nucleotide sequences to the possible binding sites of microRNA in Oryza sativa untranslated mRNA sequences revealed some significant patterns or signals such as thermodynamic properties signals, sequence architectural signals, and energy consideration which may involve directly or indirectly for the binding of microRNA in Oryza sativa .

Evidence for sequence biases associated with patterns of histone methylation

BackgroundCombinations of histone variants and modifications, conceptually representing a histone code, have been proposed to play a significant role in gene regulation and developmental processes in complex organisms. While various mechanisms have been implicated in establishing and maintaining epigenetic patterns at specific locations in the genome, they are generally believed to be independent of primary DNA sequence on a more global scale.ResultsTo address this systematically in the case of the human genome, we have analyzed primary DNA sequences underlying patterns of 19 different methylated histones in human primary T-cells and patterns of three methylated histones across additional human cell lines. We report strong sequence biases associated with most of these histone marks genome-wide in each cell type. Furthermore, the sequence characteristics for such association are distinct for different groups of histone marks.ConclusionsThese findings provide evidence of an influence of genomic sequence on patterns of histone modification associated with gene expression and chromatin programming, and they suggest that the mechanisms responsible for global histone modifications may interpret genomic sequence in various ways.

Do Femtonewton Forces Affect Genetic Function? A Review

Protein-Mediated DNA looping is intricately related to gene expression. Therefore any mechanical constraint that disrupts loop formation can play a significant role in gene regulation. Polymer physics models predict that less than a piconewton of force may be sufficient to prevent the formation of DNA loops. Thus, it appears that tension can act as a molecular switch that controls the much larger forces associated with the processive motion of RNA polymerase. Since RNAP can exert forces over 20 pN before it stalls, a 'substrate tension switch' could offer a force advantage of two orders of magnitude. Evidence for such a mechanism is seen in recent in vitro micromanipulation experiments. In this article we provide new perspective on existing theory and experimental data on DNA looping in vitro and in vivo. We elaborate on the connection between tension and a variety of other intracellular mechanical constraints including sequence specific curvature and supercoiling. In the process, we emphasize that the richness and versatility of DNA mechanics opens up a whole new paradigm of gene regulation to explore.