scholarly journals cisRED: a database system for genome-scale computational discovery of regulatory elements

2006 ◽  
Vol 34 (90001) ◽  
pp. D68-D73 ◽  
Author(s):  
G. Robertson
Keyword(s):  
Regulatory Elements ◽  
Database System ◽  
Computational Discovery ◽  
Genome Scale

scholarly journals Systematic dissection of transcriptional regulatory networks by genome-scale and single-cell CRISPR screens

2021 ◽  
Vol 7 (27) ◽  
pp. eabf5733
Author(s):  
Rui Lopes ◽  
Kathleen Sprouffske ◽  
Caibin Sheng ◽  
Esther C. H. Uijttewaal ◽  
Adriana Emma Wesdorp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regulatory Networks ◽  
Essential Role ◽  
Regulatory Elements ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory Elements ◽  
Transcriptional Regulatory ◽  
Functional Relevance ◽  
Genome Scale ◽  
Transcription Program

Millions of putative transcriptional regulatory elements (TREs) have been cataloged in the human genome, yet their functional relevance in specific pathophysiological settings remains to be determined. This is critical to understand how oncogenic transcription factors (TFs) engage specific TREs to impose transcriptional programs underlying malignant phenotypes. Here, we combine cutting edge CRISPR screens and epigenomic profiling to functionally survey ≈15,000 TREs engaged by estrogen receptor (ER). We show that ER exerts its oncogenic role in breast cancer by engaging TREs enriched in GATA3, TFAP2C, and H3K27Ac signal. These TREs control critical downstream TFs, among which TFAP2C plays an essential role in ER-driven cell proliferation. Together, our work reveals novel insights into a critical oncogenic transcription program and provides a framework to map regulatory networks, enabling to dissect the function of the noncoding genome of cancer cells.

scholarly journals Prediction of Nuclear Hormone Receptor Response Elements

2005 ◽  
Vol 19 (3) ◽  
pp. 595-606 ◽  
Author(s):  
Albin Sandelin ◽  
Wyeth W. Wasserman
Keyword(s):  
Binding Sites ◽  
Regulatory Elements ◽  
Nuclear Hormone Receptor ◽  
Regulatory Sequences ◽  
Web Interface ◽  
Model Framework ◽  
A Genome ◽  
Academic Researchers ◽  
Regulatory Potential ◽  
Genome Scale

Abstract The nuclear receptor (NR) class of transcription factors controls critical regulatory events in key developmental processes, homeostasis maintenance, and medically important diseases and conditions. Identification of the members of a regulon controlled by a NR could provide an accelerated understanding of development and disease. New bioinformatics methods for the analysis of regulatory sequences are required to address the complex properties associated with known regulatory elements targeted by the receptors because the standard methods for binding site prediction fail to reflect the diverse target site configurations. We have constructed a flexible Hidden Markov Model framework capable of predicting NHR binding sites. The model allows for variable spacing and orientation of half-sites. In a genome-scale analysis enabled by the model, we show that NRs in Fugu rubripes have a significant cross-regulatory potential. The model is implemented in a web interface, freely available for academic researchers, available at http://mordor.cgb.ki.se/NHR-scan.

scholarly journals TBIO-05. GENOME-SCALE NUCLEOTIDE-SPECIFIC CHARACTERIZATION OF 5-HYDROXYMETHYLCYTOSINE IN PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii467-iii468
Author(s):  
Nasim Azizgolshani ◽  
Curtis L Petersen ◽  
Lucas Salas ◽  
Youdinghuan Chen ◽  
Laurent Perreard ◽  
...  
Keyword(s):  
Cpg Islands ◽  
R Package ◽  
Regulatory Elements ◽  
P Value ◽  
Embryonal Tumors ◽  
Model Based Clustering ◽  
Tumor Subtypes ◽  
Increased Risk ◽  
Genome Scale ◽  
Brain Tissues

Abstract Though aberrant cytosine modifications are prevalent in cancer, nucleotide-specific 5-hydroxymethylcytosine (5hmC) modifications remain understudied, including in pediatric CNS tumors. Brain 5-hydroxymethylation is linked with development and differentiation. We measured genome-scale nucleotide-specific 5hmC in patients with diagnoses of glioma, ependymoma, and embryonal tumors under age 18 (n=36), and in non-tumor pediatric brain tissues (n=3). DNA was processed with tandem oxidative (OxBS) and bisulfite (BS) treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG sites. We used the OxyBS R package to determine levels of 5hmC and 5mC. Mean 5hmC levels were lower in tumors (gliomas 4.1%, ependymomas 3.9%, and embryonal tumors 3.4%) compared to nontumor tissues (5.3%). We subset to the CpGs with the 5% highest 5hmC content for downstream analyses (37,173 CpGs). These sites were enriched among regulatory elements, including TFBS (Odds Ratio 1.14 p-value 3.57E-20) and super-enhancers (OR 1.93, p-value 1.14E-126). Linear mixed-effects models adjusted for age, sex, and cell type proportions tested the CpG-specific differences in 5hmC between tumor and nontumor samples, as well as between tumor subtypes. 5hmC levels were depleted across tumors compared with nontumor brain tissues, including at CpG islands. Model-based clustering (RPMM) results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. Our results indicate that 5hmC localizes to sites in the DNA critical to gene regulation and is associated with patient outcomes. This study offers an opportunity to potentially contribute to classification markers for childhood brain tumors.

scholarly journals Transcriptome and translatome of CO2 fixing acetogens under heterotrophic and autotrophic conditions

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yoseb Song ◽  
Jiyun Bae ◽  
Jongoh Shin ◽  
Sangrak Jin ◽  
Jung-Kul Lee ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Anaerobic Bacteria ◽  
Regulatory Elements ◽  
Ribosome Profiling ◽  
Strain Design ◽  
Thermochemical Processes ◽  
Systematic Understanding ◽  
Growth Limits ◽  
Biochemical Production ◽  
Genome Scale

AbstractAcetogens are anaerobic bacteria that utilise gaseous feedstocks such as carbon monoxide (CO) and carbon dioxide (CO2) to synthesise biomass and various metabolites via the energetically efficient Wood-Ljungdahl pathway. Because of this pathway, acetogens have been considered as a novel platform to produce biochemicals from gaseous feedstocks, potentially replacing the conventional thermochemical processes. Despite their advantages, a lack of systematic understanding of the transcriptional and translational regulation in acetogens during autotrophic growth limits the rational strain design to produce the desired products. To overcome this problem, we presented RNA sequencing and ribosome profiling data of four acetogens cultivated under heterotrophic and autotrophic conditions, providing data on genome-scale transcriptional and translational responses of acetogens during CO2 fixation. These data facilitate the discovery of regulatory elements embedded in their genomes, which could be utilised to engineer strains to achieve better growth and productivity. We anticipate that these data will expand our understanding of the processes of CO2 fixation and will help in the designing of strains for the desired biochemical production.

scholarly journals Computational discovery of soybean promotercis-regulatory elements for the construction of soybean cyst nematode-inducible synthetic promoters

2014 ◽  
Vol 12 (8) ◽  
pp. 1015-1026 ◽  
Author(s):  
Wusheng Liu ◽  
Mitra Mazarei ◽  
Yanhui Peng ◽  
Michael H. Fethe ◽  
Mary R. Rudis ◽  
...  
Keyword(s):  
Soybean Cyst Nematode ◽  
Regulatory Elements ◽  
Cyst Nematode ◽  
Synthetic Promoters ◽  
Computational Discovery

Genome-Scale Analysis of Hematopoietic Regulatory Sequences by Digital Analysis of Chromatin Structure.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4163-4163
Author(s):  
John A. Stamatoyannopoulos ◽  
Richard Humbert ◽  
Michael Hawrylycz ◽  
James Wallace ◽  
Michael O. Dorschner ◽  
...  
Keyword(s):  
Chromatin Structure ◽  
Regulatory Elements ◽  
Regulatory Sequences ◽  
Hematopoietic Stem ◽  
Genome Wide ◽  
Hypersensitive Sites ◽  
Chromatin Structural ◽  
Tag Clustering ◽  
Genome Scale

Abstract In vivo, cis-regulatory elements coincide with focal disruptions in chromatin structure that manifest as DNaseI hypersensitive sites (HSs). We developed a novel stochastic methodology for comprehensive, genome-wide mapping of DNaseI HSs in vivo. We show that 19–20bp genomic DNA tags can be used to effect genome-wide localization of individual DNaseI cutting events in nuclear chromatin, and that such tags can be generated and sequenced in large numbers from limited numbers of starting cells. We analyzed 257,000 tags from a hematopoietic cell line (K562) and applied a quantitative algorithm to discriminate statistically significant tag clustering events. Such tag clusters identified both known and novel functional elements of hematopoietic genes across the genome. A unique feature of this approach is that it permits unbiased evaluation of the chromatin context of regulatory sequences from disperse genomic loci. We observed surprisingly large differences in the chromatin structural configuration of a variety of active erythroid and hematopoietic regulatory sequences, suggesting a discrete hierarchy of nuclear organization that is not apparent with conventional assays. This approach can be applied readily to generate a comprehensive catalogue of cis-regulatory sequences active in hematopoietic stem cells.

scholarly journals Computational discovery of regulatory elements in a continuous expression space

2012 ◽  
Vol 13 (11) ◽  
pp. R109 ◽  
Author(s):  
Mathieu Lajoie ◽  
Olivier Gascuel ◽  
Vincent Lefort ◽  
Laurent Bréhélin
Keyword(s):  
Regulatory Elements ◽  
Computational Discovery

scholarly journals Unbiased genome-scale identification of cis-regulatory modules in the human genome by GRAMc

2018 ◽  
Author(s):  
Catherine L. Guay ◽  
Jongmin Nam
Keyword(s):  
Human Genome ◽  
Dna Barcode ◽  
Cell Types ◽  
Regulatory Elements ◽  
Assay Method ◽  
Reporter Assay ◽  
Cell Type ◽  
Alu Elements ◽  
Regulatory Modules ◽  
Genome Scale

AbstractAlthough significant advances have been made toward functionally identifying human regulatory elements, existing genome-scale reporter methods preferentially detect either enhancers or promoters. Here we develop GRAMc, a highly reproducible unbiased Genome-scale Reporter Assay Method for cis-regulatory modules (CRMs). GRAMc combines the versatility of traditional reporter constructs and the scalability of DNA barcode reporters, and unites the complementary advantages of several currently available high-throughput reporter assays. We demonstrate that GRAMc can reliably measure cis-regulatory activity of nearly 90% of the human genome in 200 million HepG2 cells with randomly fragmented ~800bp inserts. By using the GRAMc-identified CRMs, we show that CRMs identified in one cell type are useful for predicting gene regulatory programs not only within that cell type but also between cell types or conditions separated in time and space. In addition, the GRAMc-identified CRMs support the hypothesis that SINE/Alu elements are rich sources of regulatory evolution. Finally, the observation that the majority of experimentally identified regulatory elements do not overlap with computationally predicted elements underscores the necessity of an efficient and unbiased genome-scale reporter assay.

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