scholarly journals Identification and characteristic analysis of enhancers across 13 major cancer types

2021 ◽  
Author(s):  
Mingming Qian ◽  
Wenzhu Wang ◽  
Yana Zhang ◽  
Yi Zhao ◽  
Huige Quan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Characteristic Analysis ◽  
Cancer Types ◽  
Highly Correlated ◽  
Functional Transcription Factor

Abstract Enhancers are often mutated and dysregulated in various diseases such as cancer. By integrating the FANTOM enhancers expression profiles and RNA-seq data from TCGA of 13 cancers and their corresponding para-cancerous tissues, we systematically identified a total of 4702 significantly differentially expressed enhancers (DE enhancers). Furthermore, a total of 1036 differentially expressed genes (DE genes) regulated by differentially expressed enhancers (DE enhancers) were identified. It was found that in these 13 cancers, most (61.13%) enhancers were ubiquitously expressed, whereas DE enhancers were more likely to be tissue-specific expressed, and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways. Finally, it was manifested that 74 SNPs located in 37 DE enhancers, and these SNPs affected the gain and loss of functional transcription factor binding sites (TFBS) of 758 transcription factors, which had been shown to be highly correlated with tumorigenesis and development.

scholarly journals Identifying Transcription Regulatory Elements in the Human and Mouse Genomes Using Tissue-specific Gene Expression Profiles

2007 ◽  
Vol 4 (2) ◽  
pp. 1-23
Author(s):  
Amitava Karmaker ◽  
Kihoon Yoon ◽  
Mark Doderer ◽  
Russell Kruzelock ◽  
Stephen Kwek
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Human And Mouse

Summary Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.

scholarly journals An exon-intron split framework to prioritize transcriptional and post-transcriptional regulatory signals and its application to study energy homeostasis in pigs

2021 ◽  
Author(s):  
Emilio Marmol-Sanchez ◽  
Susanna Cirera ◽  
Laura Zingaretti ◽  
Mette Juul Jacobsen ◽  
Yuliaxis Ramayo-Caldas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Muscle Development ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Enhancer Activity ◽  
Protein Coding ◽  
Transcriptional Regulatory ◽  
Mrna Transcripts

Bulk sequencing of RNA transcripts has typically been used to quantify gene expression levels in different experimental systems. However, linking differentially expressed (DE) mRNA transcripts to gene expression regulators, such as miRNAs or transcription factors (TFs), remains challenging, as in silico or experimental interactions are commonly identified post hoc after selecting differentially expressed genes of interest, thus biasing the interpretation of underlying gene regulatory mechanisms. In this study, we performed an exon-intron split analysis (EISA) to muscle and fat RNA-seq data from two Duroc pig populations subjected to fasting-feeding conditions and with divergent fatness profiles, respectively. We compared the number of reads from exonic and intronic regions for all expressed protein-coding genes and divided their expression profiles into transcriptional and post-transcriptional components, considering intronic and exonic fractions as estimates of the abundance of pre-mRNA and mature mRNA transcripts, respectively. In this way, we obtained a prioritized list of genes showing significant transcriptional and post-transcriptional regulatory signals. After running EISA analyses, protein-coding mRNA genes with downregulated exonic fractions and high post-transcriptional signals were significantly enriched for binding sites of upregulated DE miRNAs. Moreover, these genes showed an increased expression covariation for the exonic fraction compared to that of the intronic fraction. On the contrary, they did not show enrichment for binding sites of highly expressed and/or downregulated DE miRNAs. Among the set of loci displaying miRNA-driven post-transcriptional regulatory signals, we observed genes related to glucose homeostasis (PDK4, NR4A3, CHRNA1 and DKK2), cell differentiation (MYO9A, KLF5 and BACH2) or adipocytes metabolism (LEP, SERPINE2, RNF157, OSBPL10 and PRSS23). Besides, genes showing upregulated intronic fractions with a lack of exonic fractions were significantly enriched for TF-enhancer activity while depleted for miRNA targets, thus suggesting a transient transcription activation regulating skeletal muscle development. Our results highlight an efficient framework to classify mRNA genes showing transcriptional and post-transcriptional signals linked to transient transcription and miRNA-driven downregulation by using exonic and intronic fractions of RNA-seq datasets from muscle and adipose tissues in pigs.

scholarly journals Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Lago ◽  
Matteo Nadai ◽  
Filippo M. Cernilogar ◽  
Maryam Kazerani ◽  
Helena Domíniguez Moreno ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Gene ◽  
Open Chromatin ◽  
Rna Seq ◽  
Transcript Levels ◽  
Promoter Sequences ◽  
G Quadruplex ◽  
Cell Type Specific ◽  
Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.

scholarly journals EPEN-30. C11ORF95-RELA FUSION PROTEIN ENGAGES NOVEL GENOMIC LOCI TO DRIVE MURINE EPENDYMOMA GROWTH

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii314-iii314
Author(s):  
Amir Arabzade ◽  
Yanhua Zhao ◽  
Srinidhi Varadharajan ◽  
Hsiao-Chi Chen ◽  
Austin Stuckert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Molecular Targets ◽  
Lead Target ◽  
Open Chromatin ◽  
Rna Seq ◽  
In Utero Electroporation ◽  
Pathway Activation ◽  
Mouse Cells ◽  
Shed Light

Abstract RATIONALE Over 70% of supratentorial (ST) ependymoma are characterized by an oncogenic fusion between C11ORF95 and RELA. C11ORF95-RELA fusion is frequently the sole genetic driver detected in ST ependymoma, thus ranking this genomic event as a lead target for therapeutic investigation. RELA is a transcription factor (TF) central to mediating NF-kB pathway activation in processes such as inflammation, cellular metabolism, and chemotaxis. HYPOTHESIS: We posited that C11ORF95-RELA acts as an oncogenic TF that aberrantly shapes the tumor epigenome to drive aberrant transcription. Approach: To this end we developed an in utero electroporation (IUE) mouse model of ependymoma to express C11ORF95-RELA during embryonic development. Our IUE approach allowed us to develop C11ORF95-RELA driven tumor models and cell lines. We comprehensively characterized the epigenome and transcriptome of C11ORF95-RELA fusion driven mouse cells by H3K27ac ChIP-seq, ATAC-seq, and RNA-seq. RESULTS This data revealed that: 1) C11ORF95-RELA directly engages ‘open’ chromatin and is enriched at regions with known RELA TF binding sites as well as novel genomic loci/motifs, 2) C11ORF95-RELA preferentially binds to both H3K27ac (active) enhancers and promoters, and 3) Bound C11ORF95-RELA promoter loci are associated with increased transcription of genes shared with human ependymoma. CONCLUSION Our findings shed light on the transcriptional mechanisms of C11ORF95-RELA, and reveal downstream targets that may represent cancer dependency genes and molecular targets.

scholarly journals Persistent Interactions of Core Histone Tails with Nucleosomal DNA following Acetylation and Transcription Factor Binding

1998 ◽  
Vol 18 (11) ◽  
pp. 6293-6304 ◽  
Author(s):  
Vesco Mutskov ◽  
Delphine Gerber ◽  
Dimitri Angelov ◽  
Juan Ausio ◽  
Jerry Workman ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Molecular Biology ◽  
Binding Sites ◽  
Cross Linking ◽  
Uv Laser ◽  
Histone Tail ◽  
Histone Tails ◽  
Nucleosomal Dna ◽  
Core Histones

ABSTRACT In this study, we examined the effect of acetylation of the NH2 tails of core histones on their binding to nucleosomal DNA in the absence or presence of bound transcription factors. To do this, we used a novel UV laser-induced protein-DNA cross-linking technique, combined with immunochemical and molecular biology approaches. Nucleosomes containing one or five GAL4 binding sites were reconstituted with hypoacetylated or hyperacetylated core histones. Within these reconstituted particles, UV laser-induced histone-DNA cross-linking was found to occur only via the nonstructured histone tails and thus presented a unique tool for studying histone tail interactions with nucleosomal DNA. Importantly, these studies demonstrated that the NH2 tails were not released from nucleosomal DNA upon histone acetylation, although some weakening of their interactions was observed at elevated ionic strengths. Moreover, the binding of up to five GAL4-AH dimers to nucleosomes occupying the central 90 bp occurred without displacement of the histone NH2 tails from DNA. GAL4-AH binding perturbed the interaction of each histone tail with nucleosomal DNA to different degrees. However, in all cases, greater than 50% of the interactions between the histone tails and DNA was retained upon GAL4-AH binding, even if the tails were highly acetylated. These data illustrate an interaction of acetylated or nonacetylated histone tails with DNA that persists in the presence of simultaneously bound transcription factors.

scholarly journals HIV-1 Infection Transcriptomics: Meta-Analysis of CD4+ T Cells Gene Expression Profiles

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 244 ◽  
Author(s):  
Antonio Victor Campos Coelho ◽  
Rossella Gratton ◽  
João Paulo Britto de Melo ◽  
José Leandro Andrade-Santos ◽  
Rafael Lima Guimarães ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Differentially Expressed Genes ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Infected Cells ◽  
Hiv 1

HIV-1 infection elicits a complex dynamic of the expression various host genes. High throughput sequencing added an expressive amount of information regarding HIV-1 infections and pathogenesis. RNA sequencing (RNA-Seq) is currently the tool of choice to investigate gene expression in a several range of experimental setting. This study aims at performing a meta-analysis of RNA-Seq expression profiles in samples of HIV-1 infected CD4+ T cells compared to uninfected cells to assess consistently differentially expressed genes in the context of HIV-1 infection. We selected two studies (22 samples: 15 experimentally infected and 7 mock-infected). We found 208 differentially expressed genes in infected cells when compared to uninfected/mock-infected cells. This result had moderate overlap when compared to previous studies of HIV-1 infection transcriptomics, but we identified 64 genes already known to interact with HIV-1 according to the HIV-1 Human Interaction Database. A gene ontology (GO) analysis revealed enrichment of several pathways involved in immune response, cell adhesion, cell migration, inflammation, apoptosis, Wnt, Notch and ERK/MAPK signaling.

Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication

1992 ◽  
Vol 12 (6) ◽  
pp. 2514-2524 ◽  
Author(s):  
Z S Guo ◽  
M L DePamphilis
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Replication ◽  
Binding Sites ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Activation Domains ◽  
Auxiliary Component ◽  
Cell Extracts

The origins of DNA replication (ori) in simian virus 40 (SV40) and polyomavirus (Py) contain an auxiliary component (aux-2) composed of multiple transcription factor binding sites. To determine whether this component stimulated replication by binding specific transcription factors, aux-2 was replaced by synthetic oligonucleotides that bound a single transcription factor. Sp1 and T-antigen (T-ag) sites, which exist in the natural SV40 aux-2 sequence, provided approximately 75 and approximately 20%, respectively, of aux-2 activity when transfected into monkey cells. In cell extracts, only T-ag sites were active. AP1 binding sites could replace completely either SV40 or Py aux-2. Mutations that eliminated AP1 binding also eliminated AP1 stimulation of replication. Yeast GAL4 binding sites that strongly stimulated transcription in the presence of GAL4 proteins failed to stimulate SV40 DNA replication, although they did partially replace Py aux-2. Stimulation required the presence of proteins consisting of the GAL4 DNA binding domain fused to specific activation domains such as VP16 or c-Jun. These data demonstrate a clear role for transcription factors with specific activation domains in activating both SV40 and Py ori. However, no correlation was observed between the ability of specific proteins to stimulate promoter activity and their ability to stimulate origin activity. We propose that only transcription factors whose specific activation domains can interact with the T-ag initiation complex can stimulate SV40 and Py ori-core activity.

scholarly journals Comparative transcriptomics analysis revealing flower trichome development during flower development in two Lonicera Japonica Thunb. cultivars using RNA-seq

2020 ◽  
Author(s):  
Jianjun Li ◽  
Chenglin Ye ◽  
Cuifang Chang
Keyword(s):  
Signaling Pathways ◽  
Plant Hormones ◽  
Flower Development ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Molecular Networks ◽  
Lonicera Japonica ◽  
Rna Seq ◽  
Trichome Development ◽  
A Genome

Abstract Background: Trichomes comprise specialized multicellular structures that have the capacity to synthesize and secrete secondary metabolites and protect plants from biotic and abiotic stresses. However, little is known about the trichome formation mechanism during flower development in Lonicera Japonica Thunb.Results: Here, we present a genome-wide comparative transcriptome analysis between two L. japonica cultivars, toward the identification of biological processes and functional gene activities that occur during flowering stage trichome development. In this study, the density and average lengths of flower trichomes were at their highest during three green periods. Using the Illumina RNA-Seq method, we obtained 134,304 unigenes, 33,733 of which were differentially expressed. In an analysis of 40 differentially expressed unigenes (DEGs) involved in trichome development, 29 of these were transcription factors. The DEGs analysis of plant hormone signal transduction indicated that plant growth and development may be independent of GA and CTK signaling pathways, and plant stress may be independent of JA and ET signaling pathways. We successfully isolated key genes involved in the floral biosynthesis of odors, tastes, colors, and plant hormones, and proposed biosynthetic pathways for sesquiterpenoid, triterpenoid, monoterpenoid, flavonoid, and plant hormones. Furthermore, 82 DEGs were assigned to cell cycles and 2,616 were predicted as plant resistance genes (PRGs).Conclusions: This study provides a comprehensive characterization of the expression profiles of flower development during the seven developmental stages of L. japonica, thereby offering valuable insights into the molecular networks that underly flower development in L. japonica.

scholarly journals HOT or not: examining the basis of high-occupancy target regions

2017 ◽  
Author(s):  
Katarzyna Wreczycka ◽  
Vedran Franke ◽  
Bora Uyar ◽  
Ricardo Wurmus ◽  
Altuna Akalin
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Cell Types ◽  
Data Sets ◽  
Gene Promoters ◽  
Quadruplex Dna ◽  
Golden Standard ◽  
Multiple Cell ◽  
Multiple Species

AbstractHigh-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated genes are stably expressed across multiple cell types. Despite these features, HOT regions are solemnly defined using ChIP-seq experiments and shown to lack canonical motifs for transcription factors that are thought to be bound there. Although, ChIP-seq experiments are the golden standard for finding genome-wide binding sites of a protein, they are not noise free. Here, we show that HOT regions are likely to be ChIP-seq artifacts and they are similar to previously proposed “hyper-ChIPable” regions. Using ChIP-seq data sets for knocked-out transcription factors, we demonstrate presence of false positive signals on HOT regions. We observe sequence characteristics and genomic features that are discriminatory of HOT regions, such as GC/CpG-rich k-mers and enrichment of RNA-DNA hybrids (R-loops) and DNA tertiary structures (G-quadruplex DNA). The artificial ChIP-seq enrichment on HOT regions could be associated to these discriminatory features. Furthermore, we propose strategies to deal with such artifacts for the future ChIP-seq studies.

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