scholarly journals Identification of Transcription Factor Binding Sites Upstream of Human Genes Regulated by the Phosphatidylinositol 3-Kinase and MEK/ERK Signaling Pathways

2004 ◽  
Vol 279 (19) ◽  
pp. 20167-20177 ◽  
Author(s):  
John W. Tullai ◽  
Michael E. Schaffer ◽  
Steven Mullenbrock ◽  
Simon Kasif ◽  
Geoffrey M. Cooper
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Erk Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Human Genes ◽  
Induced Genes

We have taken an integrated approach in which expression profiling has been combined with the use of small molecule inhibitors and computational analysis of transcription factor binding sites to characterize regulatory sequences of genes that are targets of specific signaling pathways in growth factor-stimulated human cells. T98G cells were stimulated with platelet-derived growth factor (PDGF) and analyzed by DNA microarrays, which identified 74 immediate-early gene transcripts. Cells were then treated with inhibitors to identify subsets of genes that are targets of the phosphatidylinositol 3-kinase (PI3K) and MEK/ERK signaling pathways. Four groups of PDGF-induced genes were defined: independent of PI3K and MEK/ERK signaling, dependent on PI3K signaling, dependent on MEK/ERK signaling, and dependent on both pathways. The upstream regions of all genes in the four groups were scanned using TRANSFAC for putativecis-elements as compared with a background set of non-induced genes. Binding sites for 18 computationally predicted transcription factors were over-represented in the four groups of co-expressed genes compared with the background sequences (p< 0.01). Many of thecis-elements identified were conserved in orthologous mouse genes, and many of the predicted elements and their cognate transcription factors were consistent with previous experimental data. In addition, chromatin immunoprecipitation assays experimentally verified nine predicted SRF binding sites in T98G cells, including a previously unknown SRF site upstream ofDUSP5. These results indicate that groups of human genes regulated by discrete intracellular signaling pathways share commoncis-regulatory elements.

scholarly journals In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

2016 ◽  
Vol 2016 ◽  
pp. 1-27 ◽  
Author(s):  
Kristopher J. L. Irizarry ◽  
Randall L. Bryden
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Coat Color ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Color Variation ◽  
Factor Binding ◽  
Conserved Sequence ◽  
Evolutionarily Conserved

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons.

Upregulated Signaling Pathways in Ruptured Human Saccular Intracranial Aneurysm Wall: An Emerging Regulative Role of Toll-Like Receptor Signaling and Nuclear Factor-κB, Hypoxia-Inducible Factor-1A, and ETS Transcription Factors

Neurosurgery ◽  
2011 ◽  
Vol 68 (6) ◽  
pp. 1667-1676 ◽  
Author(s):  
Mitja I. Kurki ◽  
Sanna-Kaisa Häkkinen ◽  
Juhana Frösen ◽  
Riikka Tulamo ◽  
Mikael von und zu Fraunberg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Intracranial Aneurysm ◽  
Signaling Pathways ◽  
Binding Sites ◽  
Hypoxia Inducible Factor ◽  
Transcription Factor Binding Sites ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Factor Binding

Abstract BACKGROUND: Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects the working-age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. This knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. OBJECTIVE: To investigate gene expression patterns distinguishing ruptured and unruptured sIA. METHODS: We compared the whole-genome expression profile of 11 ruptured sIA wall samples with that of 8 unruptured ones using oligonucleotide microarrays. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. RESULTS: Overall, 686 genes were significantly upregulated and 740 were downregulated in the ruptured sIA walls. Significantly upregulated biological processes included response to turbulent blood flow, chemotaxis, leukocyte migration, oxidative stress, vascular remodeling; and extracellular matrix degradation. Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factor binding sites were significantly enriched among the upregulated genes. CONCLUSION: We identified pathways and candidate genes associated with the rupture of human sIA wall. Our results may provide clues to the molecular mechanism in sIA wall rupture and insight for novel therapeutic strategies to prevent rupture.

scholarly journals Different Functional Gene Clusters in Yeast have Different Spatial Distributions of the Transcription Factor Binding Sites

2011 ◽  
Vol 5 ◽  
pp. BBI.S6362 ◽  
Author(s):  
Wei-Sheng Wu
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Spatial Distribution ◽  
Transcription Factors ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Gene Clusters ◽  
Functional Gene ◽  
Spatial Distributions ◽  
Factor Binding

Transcription factors control gene expression by binding to short specific DNA sequences, called transcription factor binding sites (TFBSs), in the promoter of a gene. Thus, studying the spatial distribution of TFBSs in the promoters may provide insights into the molecular mechanisms of gene regulation. I developed a method to construct the spatial distribution of TFBSs for any set of genes of interest. I found that different functional gene clusters have different spatial distributions of TFBSs, indicating that gene regulation mechanisms may be very different among different functional gene clusters. I also found that the binding sites for different transcription factors (TFs) may have different spatial distributions: a sharp peak, a plateau or no dominant single peak. The spatial distributions of binding sites for many TFs derived from my analyses are valuable prior information for TFBS prediction algorithm because different regions of a promoter can assign different possibilities for TFBS occurrence.

scholarly journals STIFDB—Arabidopsis Stress Responsive Transcription Factor DataBase

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
K. Shameer ◽  
S. Ambika ◽  
Susan Mary Varghese ◽  
N. Karaba ◽  
M. Udayakumar ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Abiotic Stress ◽  
Stress Responses ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Stress Responsive Genes

Elucidating the key players of molecular mechanism that mediate the complex stress-responses in plants system is an important step to develop improved variety of stress tolerant crops. Understanding the effects of different types of biotic and abiotic stress is a rapidly emerging domain in the area of plant research to develop better, stress tolerant plants. Information about the transcription factors, transcription factor binding sites, function annotation of proteins coded by genes expressed during abiotic stress (for example: drought, cold, salinity, excess light, abscisic acid, and oxidative stress) response will provide better understanding of this phenomenon. STIFDB is a database of abiotic stress responsive genes and their predicted abiotic transcription factor binding sites in Arabidopsis thaliana. We integrated 2269 genes upregulated in different stress related microarray experiments and surveyed their 1000 bp and 100 bp upstream regions and 5′UTR regions using the STIF algorithm and identified putative abiotic stress responsive transcription factor binding sites, which are compiled in the STIFDB database. STIFDB provides extensive information about various stress responsive genes and stress inducible transcription factors of Arabidopsis thaliana. STIFDB will be a useful resource for researchers to understand the abiotic stress regulome and transcriptome of this important model plant system.

Role of Sp1 and HNF1 transcription factors in SGLT1 regulation during chronic intestinal inflammation

2008 ◽  
Vol 294 (6) ◽  
pp. G1354-G1361 ◽  
Author(s):  
Ramesh Kekuda ◽  
Prosenjit Saha ◽  
Uma Sundaram
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Promoter Activity ◽  
Intestinal Inflammation ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Regulatory Pathways ◽  
Factor Binding ◽  
Chronic Intestinal Inflammation

In a rabbit model of chronic intestinal inflammation, we previously demonstrated that the activity of Na-glucose cotransporter (SGLT1), SLC5A1, is inhibited. This inhibition is secondary to a decrease in the number of cotransporters, indicating that the regulation of SGLT1 during chronic inflammation is at the level of transcription. However, the regulation of SGLT1 expression and the transcription factors involved in the regulation are not yet known. In this report, we describe the cloning and characterization of rabbit SGLT1 promoter and the identification of transcription factors affected in villus cells during chronic intestinal inflammation. The promoter sequence for SGLT1 gene was identified by using the publicly available rabbit genomic sequence. Even though rabbit SGLT1 promoter did not have considerable overall homology with other mammalian SGLT1 promoters, two specificity protein 1 (Sp1) and a hepatocyte nuclear factor 1 (HNF1) binding sites were highly conserved among the species. Rabbit SGLT1 cDNA was encoded by 15 exons. Minimal promoter region determination showed that 196 nucleotides upstream of the transcription start site were sufficient for optimal promoter activity. This region encompassed two transcription factor binding sites, Sp1 and HNF1. For maximal SGLT1 promoter activity, these two transcription factor binding sites were essential, and their effect was synergistic, indicating that two separate regulatory pathways might be involved in their regulation. Using mobility shift assays, we further demonstrated that the binding of both Sp1 and HNF1 transcription factors to SGLT1 promoter regions were affected during chronic intestinal inflammation. Thus this report demonstrates that Sp1 and HNF1 transcription factors act in concert to regulate SGLT1 transcription in the chronically inflamed intestine.

Cytosine Arabinoside Substitution Decreases Transcription Factor–DNA Binding Element Complex Formation

2004 ◽  
Vol 128 (12) ◽  
pp. 1364-1371
Author(s):  
Ximbo Zhang ◽  
Frederick L. Kiechle
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Binding ◽  
Cytosine Arabinoside ◽  
Binding Sites ◽  
Binding Capacity ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Specific Transcription Factor ◽  
Factor Binding

Abstract Context.—The pyrimidine nucleoside analog, cytosine arabinoside (Ara-C), is an effective therapeutic agent for acute leukemia. The phosphorylated triphosphate, cytosine arabinoside triphosphate, competes with deoxycytosine triphosphate as a substrate for incorporation into DNA. Once incorporated into DNA, it inhibits DNA polymerase and topoisomerase I and modifies the tertiary structure of DNA. Objective.—To determine if the substitution of Ara-C for cytosine in double-stranded oligonucleotides that contain 4 specific transcription factor binding sites (TATA, GATA, C/EBP, and AP-2α) alters transcription factor binding to their respective DNA binding elements. Design.—Transcription factors were obtained from nuclear extracts from human promyelocytic leukemia HL-60 cells. [32P]-end-labeled double-stranded oligonucleotides that contained 1 or 2 specific transcription factor binding sites with or without Ara-C substitution for cytosine were used to assess transcription factor binding by electrophoretic mobility shift assay. Results.—The substitution of Ara-C for cytosine within and outside the transcription factor binding element (AP-2α, C/EBP), outside the binding element only (GATA, TATA), or within the binding element only (AP-2α) all result in a reduction in transcription factor binding to their respective DNA binding element. Conclusion.—The reduction of the binding capacity of transcription factors with their respective DNA binding elements may depend on structural changes within oligonucleotides induced by Ara-C incorporation. This altered binding capacity of transcription factors to their DNA binding elements may represent one mechanism for Ara-C cytotoxicity secondary to inhibition of transcription of new messenger RNAs and, subsequently, translation of new proteins.

Sign in / Sign up

Export Citation Format

Share Document