Identifying cis-regulatory elements by statistical analysis and phylogenetic footprinting and analyzing their coexistence and related gene ontology

2007 ◽  
Vol 31 (3) ◽  
pp. 374-384 ◽  
Author(s):  
Wei Shi ◽  
Wanlei Zhou ◽  
Dakang Xu
Keyword(s):  
Gene Ontology ◽  
Transcription Factors ◽  
Related Species ◽  
Statistical Significance ◽  
Phylogenetic Footprinting ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Computational Molecular Biology ◽  
Novel Approach ◽  
Regulation Mechanisms

Discovery of cis-regulatory elements in gene promoters is a highly challenging research issue in computational molecular biology. This paper presents a novel approach to searching putative cis-regulatory elements in human promoters by first finding 8-mer sequences of high statistical significance from gene promoters of humans, mice, and Drosophila melanogaster, respectively, and then identifying the most conserved ones across the three species (phylogenetic footprinting). In this study, a conservation analysis on both closely related species (humans and mice) and distantly related species (humans/mice and Drosophila) is conducted not only to examine more candidates but also to improve the prediction accuracy. We have found 124 putative cis-regulatory elements and grouped these into 20 clusters. The investigation on the coexistence of these clusters in human gene promoters reveals that SP1, EGR, and NRF-1 are the dominant clusters appearing in the combinatorial combination of up to five clusters. Gene Ontology (GO) analysis also shows that many GO categories of transcription factors binding to these cis-regulatory elements match the GO categories of genes whose promoters contain these elements. Compared with previous research, the contribution of this study lies not only in the finding of new cis-regulatory elements, but also in its pioneering exploration on the coexistence of discovered elements and the GO relationship between transcription factors and regulated genes. This exploration verifies the putative cis-regulatory elements that have been found from this study and also gives new insight on the regulation mechanisms of gene expression.

scholarly journals Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes

2020 ◽  
Author(s):  
Christophe Menichelli ◽  
Vincent Guitard ◽  
Rafael M. Martins ◽  
Sophie Lèbre ◽  
Jose-Juan Lopez-Rubio ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Cpg Islands ◽  
Regulatory Elements ◽  
Computational Approach ◽  
Reporter Assay ◽  
Development Stages ◽  
Regulation Mechanisms ◽  
Multicellular Organisms

AbstractLong regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER dedicated to the identification of LREs and apply it to the analysis of the genomes of different eukaryotes including P. falciparum. Our analyses show that all tested genomes contain several LREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by LREs exhibits very different behaviours depending on species and conditions. On Apicomplexa organisms, the process appears highly dynamic, with different LREs involved at different phases of their life cycle. For multicellular organisms, the same LREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, LREs appear to be of especially high importance, and our analyses show that they are involved in both transcriptomic and post-transcriptomic regulation mechanisms. Moreover, we demonstrated the biological relevance of one the LREs discovered by DExTER in P. falciparum using an in vivo reporter assay. The source code (python) of DExTER is available at address https://gite.lirmm.fr/menichelli/DExTER.

scholarly journals Epromoters function as a hub to recruit key transcription factors required for the inflammatory response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David Santiago-Algarra ◽  
Charbel Souaid ◽  
Himanshu Singh ◽  
Lan T. M. Dao ◽  
Saadat Hussain ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Inflammatory Response ◽  
Gene Clusters ◽  
Regulatory Elements ◽  
Interferon Response ◽  
Type I ◽  
Gene Promoters ◽  
Bona Fide ◽  
Distal Gene

AbstractGene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.

scholarly journals Genome-wide characterization and analysis of WRKY transcription factors in Panax ginseng

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Peng Di ◽  
Ping Wang ◽  
Min Yan ◽  
Peng Han ◽  
Xinyi Huang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Panax Ginseng ◽  
Expression Patterns ◽  
Cold Treatment ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Wrky Transcription Factors ◽  
Drought Treatment ◽  
Ginsenoside Biosynthesis ◽  
Genome Wide

Abstract Background Panax ginseng is a well-known medicinal plant worldwide. As an herbal medicine, ginseng is also known for its long lifecycle, which can reach several decades. WRKY proteins play regulatory roles in many aspects of biological processes in plants, such as responses to biotic or abiotic stress, plant development, and adaptation to environmental challenges. Genome-wide analyses of WRKY genes in P. ginseng have not been reported. Results In this study, 137 PgWRKY genes were identified from the ginseng genome. Phylogenetic analysis showed that the PgWRKYs could be clustered into three primary groups and five subgroups. Most of the PgWRKY gene promoters contained several kinds of hormone- and stress-related cis-regulatory elements. The expression patterns of PgWRKY genes in 14 different tissues were analyzed based on the available public RNA-seq data. The responses of the PgWRKY genes to heat, cold, salt and drought treatment were also investigated. Most of the PgWRKY genes were expressed differently after heat treatment, and expression trends changed significantly under drought and cold treatment but only slightly under salt treatment. The coexpression analysis of PgWRKY genes with the ginsenoside biosynthesis pathway genes identified 11 PgWRKYs that may have a potential regulatory role in the biosynthesis process of ginsenoside. Conclusions This work provides insights into the evolution, modulation and distribution of the WRKY gene family in ginseng and extends our knowledge of the molecular basis along with modulatory mechanisms of WRKY transcription factors in ginsenoside biosynthesis.

scholarly journals Endogenous retroviruses co-opted into divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

2021 ◽  
Author(s):  
Stylianos Bakoulis ◽  
Robert Krautz ◽  
Nicolas Alcaraz ◽  
Marco Salvatore ◽  
Robin Andersson
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Transposable Elements ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Endogenous Retroviruses ◽  
Gene Promoters ◽  
Specific Regulation ◽  
Regulatory Landscape

Transcription factor binding to regulatory elements is the key process underlying gene regulation during cellular differentiation. Although the specific regulation of genes by transcription factors is generally conserved, regulatory elements themselves are associated with high evolutionary turnover, a process that has been attributed to transposable elements. However, it is unclear how frequent co-option of transposable elements into regulatory elements is and to which regulatory programs they contribute. Here, we report an in-depth characterization of the transposon-derived regulatory landscape of mouse embryonic stem cells. We demonstrate that a substantial number of endogenous retroviral elements are divergently transcribed into unstable RNAs, and that these elements contribute to a sizable proportion of active enhancers and gene promoters. We further show that transposon subfamilies contribute to specific regulatory programs through their enrichment of binding sites for transcription factors, shedding light on the formation of regulatory programs and the origins of regulatory elements.

scholarly journals Mining functional annotations across species

2018 ◽  
Author(s):  
Sven Warris ◽  
Steven Dijkxhoorn ◽  
Teije van Sloten ◽  
Bart van de Vossenberg
Keyword(s):  
Gene Ontology ◽  
Related Species ◽  
Functional Annotation ◽  
Graph Database ◽  
Functional Annotations ◽  
Novel Approach

AbstractMotivationNumerous tools and databases exist to annotate and interpret the functions encoded in genomes (InterProScan, KEGG, GO etc.). However, analyzing and comparing functionality across a number of genomes, for example of related species, is not trivial.ResultsWe present a novel approach, for which KEGG and Gene Ontology data are imported into a Neo4j graph database and InterProScan results from several species are added. Using the Neo4j plugin for Cytoscape, users can query this database and visualize functional annotations (sub)graphs, to compare and group functional annotation across species.

scholarly journals Genome-wide identification of sucrose nonfermenting-1-related protein kinase (SnRK) genes in barley and RNA-seq analyses of their expression in response to abscisic acid treatment

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhiwei Chen ◽  
Longhua Zhou ◽  
Panpan Jiang ◽  
Ruiju Lu ◽  
Nigel G. Halford ◽  
...  
Keyword(s):  
Abscisic Acid ◽  
Gene Family ◽  
Stress Responses ◽  
Phylogenetic Analyses ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Related Protein ◽  
Rna Seq ◽  
Response Elements ◽  
Genome Data

Abstract Background Sucrose nonfermenting-1 (SNF1)-related protein kinases (SnRKs) play important roles in regulating metabolism and stress responses in plants, providing a conduit for crosstalk between metabolic and stress signalling, in some cases involving the stress hormone, abscisic acid (ABA). The burgeoning and divergence of the plant gene family has led to the evolution of three subfamilies, SnRK1, SnRK2 and SnRK3, of which SnRK2 and SnRK3 are unique to plants. Therefore, the study of SnRKs in crops may lead to the development of strategies for breeding crop varieties that are more resilient under stress conditions. In the present study, we describe the SnRK gene family of barley (Hordeum vulgare), the widespread cultivation of which can be attributed to its good adaptation to different environments. Results The barley HvSnRK gene family was elucidated in its entirety from publicly-available genome data and found to comprise 50 genes. Phylogenetic analyses assigned six of the genes to the HvSnRK1 subfamily, 10 to HvSnRK2 and 34 to HvSnRK3. The search was validated by applying it to Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) genome data, identifying 50 SnRK genes in rice (four OsSnRK1, 11 OsSnRK2 and 35 OsSnRK3) and 39 in Arabidopsis (three AtSnRK1, 10 AtSnRK2 and 26 AtSnRK3). Specific motifs were identified in the encoded barley proteins, and multiple putative regulatory elements were found in the gene promoters, with light-regulated elements (LRE), ABA response elements (ABRE) and methyl jasmonate response elements (MeJa) the most common. RNA-seq analysis showed that many of the HvSnRK genes responded to ABA, some positively, some negatively and some with complex time-dependent responses. Conclusions The barley HvSnRK gene family is large, comprising 50 members, subdivided into HvSnRK1 (6 members), HvSnRK2 (10 members) and HvSnRK3 (34 members), showing differential positive and negative responses to ABA.

scholarly journals Multi-omic profiling of pituitary thyrotropic cells and progenitors

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexandre Z. Daly ◽  
Lindsey A. Dudley ◽  
Michael T. Peel ◽  
Stephen A. Liebhaber ◽  
Stephen C. J. Parker ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pituitary Gland ◽  
Cell Lines ◽  
Binding Sites ◽  
Critical Factor ◽  
Regulatory Elements ◽  
Thyroid Stimulating Hormone ◽  
Neuroendocrine Cells ◽  
Bzip Transcription Factor ◽  
Enhancer Element

Abstract Background The pituitary gland is a neuroendocrine organ containing diverse cell types specialized in secreting hormones that regulate physiology. Pituitary thyrotropes produce thyroid-stimulating hormone (TSH), a critical factor for growth and maintenance of metabolism. The transcription factors POU1F1 and GATA2 have been implicated in thyrotrope fate, but the transcriptomic and epigenomic landscapes of these neuroendocrine cells have not been characterized. The goal of this work was to discover transcriptional regulatory elements that drive thyrotrope fate. Results We identified the transcription factors and epigenomic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an undifferentiated Pou1f1 lineage progenitor (GHF-T1) and a committed thyrotrope line that produces TSH (TαT1). We compared RNA-seq, ATAC-seq, histone modification (H3K27Ac, H3K4Me1, and H3K27Me3), and POU1F1 binding in these cell lines. POU1F1 binding sites are commonly associated with bZIP transcription factor consensus binding sites in GHF-T1 cells and Helix-Turn-Helix (HTH) or basic Helix-Loop-Helix (bHLH) factors in TαT1 cells, suggesting that these classes of transcription factors may recruit or cooperate with POU1F1 binding at unique sites. We validated enhancer function of novel elements we mapped near Cga, Pitx1, Gata2, and Tshb by transfection in TαT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice, and we demonstrate that GATA2 enhances Tshb expression through this element. Conclusion These results extend the ENCODE multi-omic profiling approach to the pituitary gland, which should be valuable for understanding pituitary development and disease pathogenesis. Graphical abstract

Androgen receptor: acting in the three-dimensional chromatin landscape of prostate cancer cells

2011 ◽  
Vol 5 (1) ◽  
Author(s):  
Harri Makkonen ◽  
Jorma J. Palvimo
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Binding Sites ◽  
Target Genes ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Loop Formation ◽  
Prostate Cancer Cells

AbstractAndrogen receptor (AR) acts as a hormone-controlled transcription factor that conveys the messages of both natural and synthetic androgens to the level of genes and gene programs. Defective AR signaling leads to a wide array of androgen insensitivity disorders, and deregulated AR function, in particular overexpression of AR, is involved in the growth and progression of prostate cancer. Classic models of AR action view AR-binding sites as upstream regulatory elements in gene promoters or their proximity. However, recent wider genomic screens indicate that AR target genes are commonly activated through very distal chromatin-binding sites. This highlights the importance of long-range chromatin regulation of transcription by the AR, shifting the focus from the linear gene models to three-dimensional models of AR target genes and gene programs. The capability of AR to regulate promoters from long distances in the chromatin is particularly important when evaluating the role of AR in the regulation of genes in malignant prostate cells that frequently show striking genomic aberrations, especially gene fusions. Therefore, in addition to the mechanisms of DNA loop formation between the enhancer bound ARs and the transcription apparatus at the target core promoter, the mechanisms insulating distally bound ARs from promiscuously making contacts and activating other than their normal target gene promoters are critical for proper physiological regulation and thus currently under intense investigation. This review discusses the current knowledge about the AR action in the context of gene aberrations and the three-dimensional chromatin landscape of prostate cancer cells.

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