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TICA: transcriptional Interaction and Coregulation Analyzer

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Genomics, Proteomics & Bioinformatics 2018年第5期16卷 342-353页

作者： Stefano Perna Pietro Pinoli Stefano Ceri Limsoon Wong Dipartimento di Elettronica Informazione e Bioingegneria Politecnico di Milano School of Computing National University of Singapore

transcriptional regulation is critical to cellular processes of all organisms. Regulatory mechanisms often involve more than one transcription factor(TF) from different families, binding together and attaching to the DNA as a single complex. However, only a fraction of the regulatory partners of each TF is currently known. In this paper, we present the transcriptional Interaction and Coregulation Analyzer(TICA), a novel methodology for predicting heterotypic physical interaction of TFs. TICA employs a data-driven approach to infer interaction phenomena from chromatin immunoprecipitation and sequencing(ChIP-seq) data. Its prediction rules are based on the distribution of minimal distance couples of paired binding sites belonging to different TFs which are located closest to each other in promoter regions. Notably, TICA uses only binding site information from input ChIP-seq experiments, bypassing the need to do motif calling on sequencing data. We present our method and test it on ENCODE ChIP-seq datasets, using three cell lines as reference including HepG2, GM12878, and K562. TICA positive predictions on ENCODE ChIP-seq data are strongly enriched when compared to protein complex(CORUM) and functional interaction(BioGRID) databases. We also compare TICA against both motif/ChIP-seq based methods for physical TF–TF interaction prediction and published literature. Based on our results, TICA offers significant specificity(average 0.902) while maintaining a good recall(average 0.284) with respect to CORUM, providing a novel technique for fast analysis of regulatory effect in cell lines. Furthermore, predictions by TICA are complementary to other methods for TF–TF interaction prediction(in particular, TACO and CENTDIST). Thus, combined application of these prediction tools results in much improved sensitivity in detecting TF–TF interactions compared to TICA alone(sensitivity of 0.526 when combining TICA with TACO and 0.585 when combining with CENTDIST)with little compromise in specificity(specificity 0.760 when combining

关键词： transcription factors Coregulation Protein–protein interactions Machine learning Data-driven analysis

transcriptional inhibition in Schwann cell development and nerve regeneration

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Neural Regeneration Research 2017年第8期12卷 1241-1246页

作者： Susanne Quintes Bastian G.Brinkmann Max-Planck-Institute of Experimental Medicine Department of Neurogenetics Gottingen Germany Department of Clinical Neurophysiology University Medical Center Gotingen (UMG) Gottingen Germany

Schwann cells, the myelinating glial cells of the peripheral nervous system are remarkably plastic after nerve trauma. Their transdifferentiation into specialized repair cells after injury shares some features with their development from the neural crest. Both processes are governed by a tightly regulated balance between activators and inhibitors to ensure timely lineage progression and allow re-maturation after nerve injury. Functional recovery after injury is very successful in rodents, however, in humans, lack of regeneration after nerve trauma and loss of function as the result of peripheral neuropathies represents a significant problem. Our understanding of the basic molecular machinery underlying Schwann cell maturation and plasticity has made significant progress in recent years and novel players have been discovered. While the transcriptional activators of Schwann cell development and nerve repair have been well defined, the mechanisms counteracting negative regulation of（re-）myelination are less well understood. Recently, transcriptional inhibition has emerged as a new regulatory mechanism in Schwann cell development and nerve repair. This mini-review summarizes some of the regulatory mechanisms controlling both processes and the novel concept of ＂inhibiting the inhibitors＂ in the context of Schwann cell plasticity.

关键词： Schwann cell Zeb2 myelin transcription factors regeneration remyelination neuropathy

Coordinated control of oligodendrocyte development by extrinsic and intrinsic signaling cues

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Neuroscience Bulletin 2013年第2期29卷 129-143页

作者： Li He Q.Richard Lu Department of Pediatrics and Obstetrics/Gynaecology Institute of Stem Cell and Developmental BiologyWest ChinaSecond HospitalSichuan University Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on NerveGrowth and Regeneration University of Texas Southwestern Medical Center

Oligodendrocytes, the myelin-forming cells for axon ensheathment in the central nervous system, are critical for maximizing and maintaining the conduction velocity of nerve impulses and proper brain function. Demyeli- nation caused by injury or disease together with failure of myelin regeneration disrupts the rapid propagation of action potentials along nerve fibers, and is associated with acquired and inherited disorders, including dev- astating multiple sclerosis and leukodystrophies. The molecular mechanisms of oligodendrocyte myelination and remyelination remain poorly understood. Recently, a series of signaling pathways including Shh, Notch, BMP and Wnt signaling and their intracellular effectors such as Olig1/2, Hesl/5, Smads and TCFs, have been shown to play important roles in regulating oligodendrocyte development and myelination. In this review, we summarize our recent understanding of how these signaling pathways modulate the progression of oligoden- drocyte specification and differentiation in a spatiotemporally-specific manner. A better understanding of the complex but coordinated function of extracellular signals and intracellular determinants during oligodendrocyte development will help to devise effective strategies to promote myelin repair for patients with demyelinating diseases.

关键词： oligodendrocyte specification differentiation myelination Shh, BMP, Notch and Wnt signaling transcription factors chromatin remodeling factors HDAC miRNAs

Cold signaling in plants:Insights into mechanisms and regulation

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Journal of Integrative Plant Biology 2018年第9期60卷 745-756页

作者： Xiaoyu Guo Dongfeng Liu Kang Chong Key Laboratory of Plant Molecular Physiology Institute of Botanythe Chinese Academy of SciencesBeijing 100093China University of Chinese Academy of Sciences Beijing 100049China

To survive under cold temperatures plants must be able to perceive a cold signal and transduce it into downstream components that induce appropriate defense mechanisms. In addition to inducing adaptive defenses, such as the production of osmotic factors to prevent freezing and the reprogramming of transcriptional pathways, cold temperatures induce changes in plant growth and development which can affect the plant life cycle. In this review, we summarize recent progress in characterizing cold-related genes and the pathways that allow transduction of the cold signal in plants, focusing primarily on studies in Arabidopsis tbaliana and rice （Oryza sativa）. We summarize cold perception and signal transduction from the plasma membrane to the nucleus, which involves cold sensors, calcium signals, calciumbinding proteins, mitogen-activated protein kinase cascades, and the C-repeat binding factor/dehydrationresponsive element binding pathways, as well as trehalose metabolism. Finally, we describe the balance between plant organogenesis and cold tolerance mechanisms in rice. This review encapsulates the known cold signaling factors in plants and provides perspectives for ongoing cold signaling research.

关键词： EARLY LEAF STAGE FREEZING TOLERANCE CHLOROPLAST DEVELOPMENT NEGATIVE REGULATOR transcription factors GENE-EXPRESSION ICE1 STABILITY RICE CALCIUM ARABIDOPSIS

To Gate, or Not to Gate： Regulatory Mechanisms for Intercellular Protein Transport and Virus Movement in Plants

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Molecular Plant 2011年第5期4卷 782-793页

作者： Shoko Ueki Vitaly Citovsky Institute of Plant Science and Resources Okayama University 2-20-1 Chuo Kurashiki Okayama 710-0046 Japan Department of Biochemistry and Cell Biology State University of New York Stony Brook NY 11794-5215 USA

Cell-to-cell signal transduction is vital for orchestrating the whole-body physiology of multi-cellular organ- isms, and many endogenous macromolecules, proteins, and nucleic acids function as such transported signals. In plants, many of these molecules are transported through plasmodesmata （Pd）, the cell wall-spanning channel structures that interconnect plant cells. Furthermore, Pd also act as conduits for cell-to-cell movement of most plant viruses that have evolved to pirate these channels to spread the infection. Pd transport is presumed to be highly selective, and only a limited repertoire of molecules is transported through these channels. Recent studies have begun to unravel mechanisms that actively regulate the opening of the Pd channel to allow traffic. This macromolecular transport between cells comprises two consecutive steps： intracellular targeting to Pd and translocation through the channel to the adjacent cell. Here, we review the current knowledge of molecular species that are transported though Pd and the mechanisms that control this traffic. Generally, Pd traffic can occur by passive diffusion through the trans-Pd cytoplasm or through the membrane/lu- men of the trans-Pd ER, or by active transport that includes protein-protein interactions. It is this latter mode of Pd trans- port that is involved in intercellular traffic of most signal molecules and is regulated by distinct and sometimes interdependent mechanisms, which represent the focus of this article.

关键词： Plasmodesmata cell-to-cell transport plant viruses transcription factors

Comprehensive Analysis of Expressed Sequence Tags from the Pulp of the Red Mutant ‘Cara Cara’ Navel Orange (Citrus sinensis Osbeck)

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Journal of Integrative Plant Biology 2010年第10期52卷 856-867页

作者： Jun-Li Ye An-Dan Zhu Neng-Guo Tao Qiang Xu Juan Xu Xiu-Xin Deng National Key Laboratory of Crop Genetic Improvement National Center of Citrus Breeding Huazhong Agricultural University Wuhan430070 China

Expressed sequence tag （EST） analysis of the pulp of the red-fleshed mutant ＇Cara Cara＇ navel orange provided a starting point for gene discovery and transcriptome survey during citrus fruit maturation. interpretation of the EST datasets revealed that the mutant pulp transcriptome held a high section of stress responses related genes, such as the type III metallothionein-like gene （6.0%）, heat shock protein （2.8%）, Cu/Zn superoxide dismutase （0.8%）, late embryogenesis abundant protein 5 （0.8%）, etc. 133 transcripts were detected to be differentially expressed between the red mutant and its orange-color wild genotype ＇Washington＇ via digital expression analysis. Among them, genes involved in metabolism, defense/stress and signal transduction were statistical overrepresented. Fifteen transcription factors, composed of NAM, ATAF, and CUC transcription factor （NAC）; myeloblastosis （MYB）; myelocytomatosis （MYC）; basic helix-loop-helix （bHLH）; basic leucine zipper （bZIP） domain members, were also included. The data reflected the distinct expression profile and the unique regulatory module associated with these two genotypes. Eight differently expressed genes analyzed in digital were validated by quantitative real- time polymerase chain reaction. For structural polymorphism, both simple sequence repeats and single nucleotide polymorphisms （SNP） loci were surveyed; dinucleotide presentation revealed a bias toward AG/GA/TC/CT repeats （52.5%）, against GC/CG repeats （0%）. SNPs analysis found that transitions （73%） outnumbered transversions （27%）. Seventeen potential cultivar-specific and 387 heterozygous SNP loci were detected from ＇Cara Cara＇ and ＇Washington＇ EST pool.

关键词： Surveys Surveying Sweet oranges Genes Pulp Pulping Mutants Gas chromatography transcription factors Copper

Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance

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Journal of Animal Science and Biotechnology 2021年第1期12卷 1-36页

作者： Massimo Bionaz Einar Vargas-Bello-Pérez Sebastiano Busato Department of Animal and Rangeland Sciences Oregon State UniversityCorvallisOR 97331USA Department of Veterinary and Animal Sciences Faculty of Health and Medical SciencesUniversity of CopenhagenGrønnegårdsvej 3DK-1870 Frederiksberg CDenmark.

High producing dairy cows generally receive in the diet up to 5–6% of fat. This is a relatively low amount of fat in the diet compared to diets in monogastrics;however, dietary fat is important for dairy cows as demonstrated by the benefits of supplementing cows with various fatty acids(FA). Several FA are highly bioactive, especially by affecting the transcriptome;thus, they have nutrigenomic effects. In the present review, we provide an up-to-date understanding of the utilization of FA by dairy cows including the main processes affecting FA in the rumen,molecular aspects of the absorption of FA by the gut, synthesis, secretion, and utilization of chylomicrons;uptake and metabolism of FA by peripheral tissues, with a main emphasis on the liver, and main transcription factors regulated by FA. Most of the advances in FA utilization by rumen microorganisms and intestinal absorption of FA in dairy cows were made before the end of the last century with little information generated afterwards. However,large advances on the molecular aspects of intestinal absorption and cellular uptake of FA were made on monogastric species in the last 20 years. We provide a model of FA utilization in dairy cows by using information generated in monogastrics and enriching it with data produced in dairy cows. We also reviewed the latest studies on the effects of dietary FA on milk yield, milk fatty acid composition, reproduction, and health in dairy cows. The reviewed data revealed a complex picture with the FA being active in each step of the way, starting from influencing rumen microbiota, regulating intestinal absorption, and affecting cellular uptake and utilization by peripheral tissues, making prediction on in vivo nutrigenomic effects of FA challenging.

关键词： Absorption Dairy cow Dietary fatty acids Intestine Liver Metabolism Performance transcription factors Transport

transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity

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Neuroscience Bulletin 2017年第1期33卷 85-94页

作者： Ying Wang Wen-Yuan Li Zhi-Gang Li Li-Xin Guan Ling-Xiao Deng Department of Anatomy Mudanjiang College of MedicineMudanjiang 157011 China Department of General Surgery First Affiliated Hospital of Mudanjiang College of Medicine Mudanjiang 157011 China Department of Pharmacy Mudanjiang College of MedicineMudanjiang 157011 China Spinal Cord and Brain Injury Research Group Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis IN 46202 USA

Injury to the nervous system induces localized damage in neural structures and neuronal death through the primary insult, as well as delayed atrophy and impaired plasticity of the delicate dendritic fields necessary for intemeuronal communication. Excitotoxicity and other sec- ondary biochemical events contribute to morphological changes in neurons following injury. Evidence suggests that various transcription factors are involved in the dendritic response to injury and potential therapies. transcription factors play critical roles in the intracellular regulation of neuronal morphological plasticity and dendritic growth and patteming. Mounting evidence supports a crucial role for epigenetic modifications via histone deacetylases, histone acetyltransferases, and DNA methyltransferases that modify gene expression in neuronal injury and repair processes. Gene regulation through epigenetic modification is of great interest in neurotrauma research, and an early picture is beginning to emerge conceming how injury triggers intracellular events that modulate such responses. This review provides an overview of injury-mediated influences on transcriptional regulation through epigenefic modification, the intracellular processes involved in the morphological consequences of such changes, and potential approaches to the therapeutic manipulation of neuronal epigenetics for regulating gene expression to facilitate growth and signaling through dendritic arborization following injury.

关键词： Nervous system injury Dendrite plasticity transcription factors Epigenetics

Genomic basis for light control of plant development

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Protein & Cell 2012年第2期3卷 106-116页

作者： Jigang Li William Terzaghi Xing Wang Deng Peking-Yale Joint Center for Plant Molecular Genetics and Agro-biotechnology State Key Laboratory of Protein and Plant Gene ResearchCollege of Life SciencesPeking UniversityBeijing 100871China Department of Molecular Cellularand Developmental BiologyYale UniversityNew HavenCT06520-8104USA Department of Biology Wilkes UniversityWilkes-BarrePA18766USA

Light is one of the key environmental signals regulating plant growth and development.Therefore,understanding the mechanisms by which light controls plant development has long been of great interest to plant biologists.Traditional genetic and molecular approaches have successfully identified key regulatory factors in light signaling,but recent genomic studies have revealed massive reprogramming of plant transcriptomes by light,identified binding sites across the entire genome of several pivotal transcription factors in light signaling,and discovered the involvement of epigenetic regulation in light-regulated gene expression.This review summarizes the key genomic work conducted in the last decade which provides new insights into light control of plant development.

关键词： light control of plant development photomorphogenesis gene expression epigenomic regulation transcription factors