scholarly journals Gene Regulation by CcpA and Catabolite Repression Explored by RNA-Seq in Streptococcus mutans

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e60465 ◽  
Author(s):  
Lin Zeng ◽  
Sang Chul Choi ◽  
Charles G. Danko ◽  
Adam Siepel ◽  
Michael J. Stanhope ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Streptococcus Mutans ◽  
Catabolite Repression ◽  
Rna Seq

scholarly journals Transcriptome Response to Drought, Rehydration and Re-Dehydration in Potato

2019 ◽  
Vol 21 (1) ◽  
pp. 159 ◽  
Author(s):  
Yongkun Chen ◽  
Canhui Li ◽  
Jing Yi ◽  
Yu Yang ◽  
Chunxia Lei ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Gene Regulation ◽  
Lipid Metabolism ◽  
Drought Stress ◽  
Sugar Metabolism ◽  
Rna Seq ◽  
Drought Tolerant ◽  
Cell Components ◽  
Drought Hardening

Potato is an important food crop and its production is susceptible to drought. Drought stress in crop growth is usually multiple- or long-term. In this study, the drought tolerant potato landrace Jancko Sisu Yari was treated with drought stress, rehydration and re-dehydration, and RNA-seq was applied to analyze the characteristics of gene regulation during these treatments. The results showed that drought-responsive genes mainly involved photosynthesis, signal transduction, lipid metabolism, sugar metabolism, wax synthesis, cell wall regulation, osmotic adjustment. Potato also can be recovered well in the re-emergence of water through gene regulation. The recovery of rehydration mainly related to patatin, lipid metabolism, sugar metabolism, flavonoids metabolism and detoxification besides the reverse expression of the most of drought-responsive genes. The previous drought stress can produce a positive responsive ability to the subsequent drought by drought hardening. Drought hardening was not only reflected in the drought-responsive genes related to the modified structure and cell components, but also in the hardening of gene expression or the “memory” of drought-responsive genes. Abundant genes involved photosynthesis, signal transduction, sugar metabolism, protease and protease inhibitors, flavonoids metabolism, transporters and transcription factors were subject to drought hardening or memorized drought in potato.

scholarly journals RBPMetaDB: A comprehensive annotation of mouse RNA-Seq datasets with perturbations of RNA-binding proteins

2018 ◽  
Author(s):  
Jin Li ◽  
Su-Ping Deng ◽  
Jacob Vieira ◽  
James Thomas ◽  
Valerio Costa ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Dna Binding ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Experimental Studies ◽  
Easy Access ◽  
Rna Seq ◽  
Mrna Stabilization

AbstractRNA-binding proteins may play a critical role in gene regulation in various diseases or biological processes by controlling post-transcriptional events such as polyadenylation, splicing, and mRNA stabilization via binding activities to RNA molecules. Due to the importance of RNA-binding proteins in gene regulation, a great number of studies have been conducted, resulting in a large amount of RNA-Seq datasets. However, these datasets usually do not have structured organization of metadata, which limits their potentially wide use. To bridge this gap, the metadata of a comprehensive set of publicly available mouse RNA-Seq datasets with perturbed RNA-binding proteins were collected and integrated into a database called RBPMetaDB. This database contains 278 mouse RNA-Seq datasets for a comprehensive list of 163 RNA-binding proteins. These RNA-binding proteins account for only ∼10% of all known RNA-binding proteins annotated in Gene Ontology, indicating that most are still unexplored using high-throughput sequencing. This negative information provides a great pool of candidate RNA-binding proteins for biologists to conduct future experimental studies. In addition, we found that DNA-binding activities are significantly enriched among RNA-binding proteins in RBPMetaDB, suggesting that prior studies of these DNA- and RNA-binding factors focus more on DNA-binding activities instead of RNA-binding activities. This result reveals the opportunity to efficiently reuse these data for investigation of the roles of their RNA-binding activities. A web application has also been implemented to enable easy access and wide use of RBPMetaDB. It is expected that RBPMetaDB will be a great resource for improving understanding of the biological roles of RNA-binding proteins.Database URL: http://rbpmetadb.yubiolab.org

scholarly journals Terminitor: Cleavage Site Prediction Using Deep Learning Models

2019 ◽  
Author(s):  
Chen Yang ◽  
Chenkai Li ◽  
Ka Ming Nip ◽  
René L Warren ◽  
Inanc Birol
Keyword(s):  
Experimental Data ◽  
Gene Regulation ◽  
Deep Learning ◽  
Cleavage Site ◽  
Differential Expression Analysis ◽  
Underlying Mechanism ◽  
Library Preparation ◽  
Rna Seq ◽  
Sequencing Data ◽  
Reference Transcriptome

AbstractAs a widespread RNA processing machinery, alternative polyadenylation plays a crucial role in gene regulation. To help decipher its underlying mechanism and understand its impact, it is desirable to comprehensively profile 3’-untranslated region cleavage and associated polyadenylation sites. State-of-the-art polyadenylation site detection tools are known to be influenced by library preparation artefacts or manually selected features. Moreover, recently published machine learning methods have only been tested on pre-constructed datasets, thus lacking validation on experimental data. Here we present Terminitor, the first deep neural network-based profiling pipeline to make predictions from RNA-seq data. We show how Terminitor outperforms competing tools in sensitivity and precision on experimental transcriptome sequencing data, and demonstrate its use with data from short- and long-read sequencing technologies. For species without a good reference transcriptome annotation, Terminitor is still able to pass on the information learnt from a related species and make reasonable predictions. We used Terminitor to showcase how single nucleotide variations can create or destroy polyadenylated cleavage sites in human RNA-seq samples.Author Summary3’ cleavage and polyadenylation of pre-mRNA is part of RNA maturation process. One gene can be cleaved at different positions at its 3’ end, namely alternatively polyadenylation, thus identifying the correct polyadenylated cleavage site (poly(A) CS) is essential to unveil its role in gene regulation under different physiological and pathological conditions. The current poly(A) CS prediction tools are either heavily influenced by RNA-Seq library preparation artefacts or have only been designed and tested on ad hoc datasets, lacking association with real world applications. In this study, we present a deep learning model, Terminitor, that predicts the probability of a nucleotide sequence containing a poly(A) CS, and validated its performance on human and mouse data. Along with the model, we propose a poly(A) CS profiling pipeline for RNA-seq data. We benchmarked our pipeline against competing tools and achieved higher sensitivity and precision in experimental data. The usage of Terminitor is not limited to genome and transcriptome annotation and we expect it to facilitate the identification of novel isoforms, improve the accuracy of transcript quantification and differential expression analysis, and contribute to the repertoire of reference transcriptome annotation.

scholarly journals Gene regulation inference from single-cell RNA-seq data with linear differential equations and velocity inference

2018 ◽  
Author(s):  
Pierre-Cyril Aubin-Frankowski ◽  
Jean-Philippe Vert
Keyword(s):  
Gene Regulation ◽  
Single Cell ◽  
De Novo ◽  
State Of The Art ◽  
Real Data ◽  
Biological Processes ◽  
Rna Seq ◽  
Cell Cycles ◽  
Linear Differential ◽  
Cell Trajectories

AbstractSingle-cell RNA sequencing (scRNA-seq) offers new possibilities to infer gene regulation networks (GRN) for biological processes involving a notion of time, such as cell differentiation or cell cycles. It also raises many challenges due to the destructive measurements inherent to the technology. In this work we propose a new method named GRISLI for de novo GRN inference from scRNA-seq data. GRISLI infers a velocity vector field in the space of scRNA-seq data from profiles of individual data, and models the dynamics of cell trajectories with a linear ordinary differential equation to reconstruct the underlying GRN with a sparse regression procedure. We show on real data that GRISLI outperforms a recently proposed state-of-the-art method for GRN reconstruction from scRNA-seq data.

Nitrogen metabolite repression in Aspergillus nidulans: an historical perspective

1995 ◽  
Vol 73 (S1) ◽  
pp. 148-152 ◽  
Author(s):  
Herbert N. Arst Jr.
Keyword(s):  
Gene Regulation ◽  
Aspergillus Nidulans ◽  
Catabolite Repression ◽  
Historical Perspective ◽  
Carbon Catabolite Repression ◽  
Growth Inhibitors ◽  
Nitrogen Metabolite Repression ◽  
The Past ◽  
Regulatory Mutations ◽  
Key Words Aspergillus

The paper of Arst and Cove (Mol. Gen. Genet. 126: 111 – 141, 1973) on "Nitrogen metabolite repression in Aspergillus nidulans" has influenced studies and perceptions of gene regulation in filamentous fungi during the past 21 years. Here I attempt to appraise the contributions of that paper and assess its role in further developments. Nitrogen metabolite repression, carbon catabolite repression, pathway-specific and integrated induction, as-acting regulatory mutations, a useful class of growth inhibitors, and a homologous Neurospora crassa gene are all discussed. Key words: Aspergillus nidulans, carbon catabolite repression, nitrogen metabolite repression.

scholarly journals Conserved units of co-expression in bacterial genomes: an evolutionary insight into gene regulation

2014 ◽  
Author(s):  
Ivan Junier ◽  
Olivier Rivoire
Keyword(s):  
Gene Regulation ◽  
Strongly Correlated ◽  
Rna Seq ◽  
Regulatory Factor ◽  
Bacterial Genomes ◽  
Promoter Regions ◽  
Dna And Rna ◽  
Genome Wide ◽  
Associated Proteins ◽  
Underlying Mechanisms

Genome-wide measurements of transcriptional activity in bacteria indicate that the transcription of successive genes is strongly correlated beyond the scale of operons. However, the underlying mechanisms are poorly characterized and a systematic method for identifying local groups of co-transcribed genes is lacking. Here, we identify supra-operonic segments of consecutive genes by comparing gene proximity in thousands of bacterial genomes. Structurally, the segments are contained within micro-domains delineated by known nucleoid-associated proteins, and they contain operons with specific relative orientations. Functionally, the operons within a same segment are highly co-transcribed, even in the absence of regulatory factors at their promoter regions. Hence, operons with no common regulatory factor can be co-regulated if they share a regulatory factor at the level of segments. To rationalize these findings, we put forward the hypothesis supported by RNA-seq data that facilitated co-transcription, the feedback of transcription into itself involving only DNA and RNA-polymerases, may represent both an evolutionary primitive and a functionally primary mode of gene regulation.

scholarly journals ANNOgesic: A Swiss army knife for the RNA-Seq based annotation of bacterial/archaeal genomes

2017 ◽  
Author(s):  
Sung-Huan Yu ◽  
Jörg Vogel ◽  
Konrad U. Förstner
Keyword(s):  
Gene Regulation ◽  
Genome Annotation ◽  
Genomic Sequence ◽  
High Accuracy ◽  
Rna Seq ◽  
Coding Sequences ◽  
Genomic Features ◽  
Non Coding Rnas ◽  
Genome Annotations ◽  
Integrate Data

AbstractTo understand the gene regulation of an organism of interest, a comprehensive genome annotation is essential. While some features, such as coding sequences, can be computationally predicted with high accuracy based purely on the genomic sequence, others, such as promoter elements or non-coding RNAs are harder to detect. RNA-Seq has proven to be an efficient method to identify these genomic features and to improve genome annotations. However, processing and integrating RNA-Seq data in order to generate high-resolution annotations is challenging, time consuming and requires numerous different steps. We have constructed a powerful and modular tool called ANNOgesic that provides the required analyses and simplifies RNA-Seq-based bacterial and archaeal genome annotation. It can integrate data from conventional RNA-Seq and dRNA-Seq, predicts and annotates numerous features, including small non-coding RNAs, with high precision. The software is available under an open source license (ISCL) at https://pypi.org/project/ANNOgesic/.

scholarly journals Downregulation of SETD2-H3K36me3 Tumor Suppression Axis Promotes MLL Leukemia through Activation of DOT1L-H3K79me2 Axis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 435-435
Author(s):  
Jiachen Bu ◽  
Aili Chen ◽  
Yunzhu Dong ◽  
Fuhong He ◽  
Xiaomei Yan ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Mouse Model ◽  
Histone H3 ◽  
The Body ◽  
Single Mutation ◽  
Rna Seq ◽  
Expression Levels ◽  
Gene Dysregulation ◽  
The Impact

Abstract SET domain containing 2 (SETD2) gene encodes the sole methyltransferase that is specific for histone H3 lysine 36 trimethylation (H3K36me3) in mammals. Previously we identified somatic SETD2 loss-of-function (LOF) mutations in both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patients. Interestingly, SETD2 mutations were identified in over 20% of leukemia patients with MLL gene rearrangement. Using an Mll-Af9 (MA9) knock-in AML mouse model, we found that downregulation of Setd2 by shRNA or genetic knock-out/knock-in strategies significantly accelerated disease development. However, the contribution of SETD2-H3K36me3 axis downregulation to MLL leukemia progression has not yet been fully understood. In MLL leukemia, high expression levels of MLL targets, driven by aberrant histone H3 lysine 79 dimethylation (H3K79me2), have been reported. Both H3K36me3 and H3K79me2 are enriched within the body of transcriptionally active genes and are associated with phosphorylated RNA Polymerase II. Whether H3K36me3 also contributes to gene dysregulation in MLL leukemia, whether SETD2-H3K36me3 downregulation has impacts on DOT1L-H3K79me2 axis, and how it promotes MLL leukemia progression are unclear. More importantly, SETD2 mutations were enriched in relapsed B-cell ALL patients. SETD2 LOF mutation could cause chemotherapy resistance or relapse after bone marrow transplantation. Thus, mechanistic-driven novel therapies are urgently needed for leukemia with SETD2 mutation. Firstly, to understand SETD2-H3K36me3 axis on gene regulation in MLL leukemia, we purified c-Kit+ hematopoietic stem/progenitor cells (HSPCs) fromMA9 and normal C57/BL/6 wild-type (WT) adult mice. Using immuno-blotting, we found increased H3K36me3 and H3K79me2 in the HSPCs from MA9 compared to those from WT mice. To further study the global histone modification and gene regulation, we performed ChIP-seq and RNA-seq analyses. Genome-wide increase of H3K36me3 and H3K79me2 were confirmed in the HSPCs from MA9 mice, and both modifications were positively correlated with gene expression. Our results indicate that not only increased H3K79me2, but also increased H3K36me3 are related to gene dysregulation in MLL leukemogenesis. Next, to explore the impact of SETD2-H3K36me3 loss on DOT1L-H3K79me2 axis and leukemia progression, we performed KD of Setd2 gene. Setd2 KD caused increased self-renewal and proliferation abilities of both WT and MA9 HSPCs. However, Setd2 KD-WT HSPCs could be replated only 3-4 times in vitro, suggesting that the SETD2 single mutation is not sufficient for leukemic transformation. In contrast, Setd2 KD significantly enhanced in vitro replating ability and in vivo leukemia development of MA9 HSPCs. Immuno-blotting and ChIP-seq results revealed the dramatic loss of H3K36me3 in Setd2 KD cells. Surprisingly, global H3K79me2 was further increased in Setd2 KD cells. As upregulation of MLL targets is the main driver for MLL leukemogenesis, we measured the expression levels of known MLL targets. However, no significant change was found either in the RNA-seq or qPCR validation. Moreover, up-regulated genes with higher H3K79me2 in their 5' gene bodies were not enriched in the classical known MLL targets but a different group of AML related genes including Arg, Erg and Bcl2l1. This partially explains the corporative activity between SETD2 LOF and MLL fusions. Thirdly, due to the further increase of H3K79me2 in Setd2 KD cells, we tested epigenetic inhibitors for DOT1L-H3K79me2 axis in MLL leukemia with SETD2 LOF mutant models. DOT1L inhibitor EPZ-5676 induced differentiation and cell death of Setd2 KD MA9 cellsor MA9/Setd2 LOF mutant cells with significantly lower concentration (450nM) compared to the case of MA9 cells (1000nM), indicating that DOT1L-H3K79me2 axis could be the tumor vulnerability of this chemo-resistant type of leukemia. In conclusion, using MA9 genetic knock-in mouse model and modulating SETD2-H3K36me3 axis, we found that, 1) not only H3K79me2, but also H3K36me3 were aberrantly modified in MLL leukemia which related to gene dysregulation, 2) Downregulation of SETD2-H3K36me3 axis could further upregulate DOT1L-H3K79me2 axis, leading to activation of a new set of AML related genes which could contributes to quick leukemia onset, 3) EPZ-5676 could be an effective therapeutic option for MLL leukemia patients with SETD2 mutations by targeting its tumor vulnerability. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effects of larval density on gene regulation in C. elegans during routine L1 synchronization

2018 ◽  
Author(s):  
Io Long Chan ◽  
Oliver J. Rando ◽  
Colin C. Conine
Keyword(s):  
Gene Regulation ◽  
Larval Density ◽  
Low Density ◽  
Rna Seq ◽  
C Elegans ◽  
Signalling Molecule ◽  
Gfp Reporter ◽  
Short Period ◽  
Early Developmental ◽  
Single Worm

ABSTRACTBleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signalling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes in our dataset – lips-15 – and confirmed that this reporter was expressed specifically in worms arrested at relatively low density. Finally, we show that conditioned media from high density L1 cultures was able to downregulate lips-15 even in L1 animals arrested at low density, and experiments using daf-22 mutant animals demonstrated that this effect is not mediated by the ascaroside family of signalling pheromones. Together, our data implicate a soluble signalling molecule in density sensing by L1 stage C. elegans, and provide guidance for design of experiments focused on early developmental gene regulation.

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