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Genome-Wide Signatures of Transcription Factor Activity: Connecting Transcription Factors, Disease, and Small Molecules

Jing Chen, Zhen Hu, Mukta Phatak, John Reichard, Johannes M. Freudenberg, Siva Sivaganesan, Mario Medvedovic, Quaid Morris
2013 PLoS Computational Biology  
Through a large study of disease-related transcriptional signatures and transcriptional signatures of drug activity, we demonstrate that increase in statistical power associated with the use of TREG signatures  ...  We developed a statistical framework for constructing genome-wide signatures of TF activity, and for using such signatures in the analysis of gene expression data produced by complex transcriptional regulatory  ...  Using TREG signatures to connect small molecules, transcription factors, and disease.  ... 
doi:10.1371/journal.pcbi.1003198 pmid:24039560 pmcid:PMC3764016 fatcat:g7qfdioztzf6lpk6c6s75uhdgi

Transcriptome-wide signatures of tumor stage in kidney renal clear cell carcinoma: connecting copy number variation, methylation and transcription factor activity

Qi Liu, Pei-Fang Su, Shilin Zhao, Yu Shyr
2014 Genome Medicine  
Unlike genetic and epigenetic alterations, however, activity changes of transcription factors, generally occurring at the post-transcriptional or post-translational level, are hard to detect and quantify  ...  Methods: Here we developed a statistical framework to infer the activity changes of transcription factors by simultaneously taking into account the contributions of genetic and epigenetic alterations to  ...  Acknowledgements The authors wish to thank reviewers for valuable comments and Margot Bjoring for editorial work on this manuscript.  ... 
doi:10.1186/s13073-014-0117-z pmid:25648588 pmcid:PMC4293006 fatcat:hvdy3gsmmfb5fao737ynmlmvau

Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma

Bin Yan, Xinping Yang, Tin-Lap Lee, Jay Friedman, Jun Tang, Carter Van Waes, Zhong Chen
2007 Genome Biology  
The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, nuclear factor-κB (NF-κB), activator protein (AP)-1, signal transducer  ...  Results: Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures that distinguished cancer cell subsets associated with p53 status.  ...  We are grateful to Drs Thomas E Carey and Carol R Bradford (University of Michigan, Ann Harbor, MI, USA) for providing UM-SCC cell lines and related clinical data.  ... 
doi:10.1186/gb-2007-8-5-r78 pmid:17498291 pmcid:PMC1929156 fatcat:5genest4anacrjpwb7snmiufue

Can Systems Biology Understand Pathway Activation? Gene Expression Signatures as Surrogate Markers for Understanding the Complexity of Pathway Activation

Hiraku Itadani, Shinji Mizuarai, Hidehito Kotani
2008 Current Genomics  
Genome-wide mutational analysis of cancer genes in individual tumors is the most direct way to elucidate the complex process of disease progression, although such high-throughput sequencing technologies  ...  In this review, we will discuss recent studies on the development of expression signatures to monitor signaling pathway activities and how these signatures can be used to improve the identification of  ...  Transcription factors in DEGs repress the activity of AP-1 and EGR1 to attenuate their own transcription as a negative feedback.  ... 
doi:10.2174/138920208785133235 pmid:19517027 pmcid:PMC2694555 fatcat:bgy3ddmd4bh2tguw34gkh622iu

Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer

Diana Mechtcheriakova, Martin Svoboda, Anastasia Meshcheryakova, Erika Jensen-Jarolim
2012 Cancer Immunology and Immunotherapy  
Th2-driven inflammation and (2) to what extent may aberrant AID in human non-B cells lead to abnormal cell state associated with an increased rate of genomic alterations as point mutations, small insertions  ...  Despite ongoing progress, the complete understanding of fundamental aspects is still lacking as (1) what are the crucial factors triggering an aberrant AID expression/ activity including the impact of  ...  and the source are credited.  ... 
doi:10.1007/s00262-012-1255-z pmid:22527246 pmcid:PMC3427704 fatcat:7yojy52ejjgvzobcqpyhe6nqoa

Network analysis reveals a causal role of mitochondrial gene activity in atherosclerotic lesion formation

Baiba Vilne, Josefin Skogsberg, Hassan Foroughi Asl, Husain Ahammad Talukdar, Thorsten Kessler, Johan L.M. Björkegren, Heribert Schunkert
2017 Atherosclerosis  
Within these modules, we identified the transcription factor estrogen related receptor (ERR)-a and its cofactors PGC1-a and -b, i.e. two members of the peroxisome proliferator-activated receptor g co-activator  ...  Co-expression network analysis revealed that both mitochondrial signature genes were highly connected in two modules, negatively correlating with lesion size and supported as causal for coronary artery  ...  factor-binding sites (TFBS), as well as small molecule-gene associations.  ... 
doi:10.1016/j.atherosclerosis.2017.10.019 pmid:29100060 fatcat:sfkxygw7n5fu5axrnjd6vqxf6i

Genomic approaches to small molecule discovery

K Stegmaier
2009 Leukemia  
It will focus on the use of genomic tools to discover cancer targets and the development and application of both cell-based and in silico gene expressionbased approaches to small molecule discovery.  ...  A logical next step is the integration of genomic approaches into small molecule discovery.  ...  Acknowledgements The Stegmaier laboratory is supported by the US National Institutes of Health, the Howard Hughes Medical Institute Physician Scientist Early Career Award, the Leukemia and Lymphoma Society  ... 
doi:10.1038/leu.2009.29 pmid:19262600 fatcat:5kmdxgazpfhy7huztpucmsy4mu

Mechanisms regulating zygotic genome activation

Katharine N. Schulz, Melissa M. Harrison
2018 Nature reviews genetics  
Recent work highlights the central role of transcriptional activators and suggests that these factors may coordinate transcriptional activation with other developmental changes.  ...  However, we still lack a full mechanistic understanding of how genome activation is executed and how this activation relates to the reprogramming of the zygotic chromatin architecture.  ...  Acknowledgements We would like to thank members of the Harrison lab and the reviewers for helpful feedback on the manuscript.  ... 
doi:10.1038/s41576-018-0087-x pmid:30573849 pmcid:PMC6558659 fatcat:s5qv7t74ubeqdho4o27hyc7duu

Genomics-guided drawing of malignant regulatory signatures revealed a pivotal role of human stem cell-associated retroviral sequences (SCARS) and functionally-active hESC enhancers [article]

Gennadi Glinsky
2020 arXiv   pre-print
Contemporary evidence are presented that high-fidelity molecular signals of continuing activities of SCARS in association with genomic regulatory networks of thousands functionally-active enhancers triggering  ...  SCARS represent evolutionary- and biologically-related family of genomic regulatory sequences, the principal physiological function of which is to create and maintain the stemness phenotype during human  ...  Activation of transcription at SCARS loci and production of SCARS RNAs. 3. Activation of a genome-wide network of functional enhancers associated with a pluripotent state. 4.  ... 
arXiv:2008.00687v1 fatcat:jdowrxwdzvg65bxbcw7kq5oofe

An Integrated Bioinformatics Approach Identifies Elevated Cyclin E2 Expression and E2F Activity as Distinct Features of Tamoxifen Resistant Breast Tumors

Lei Huang, Shuangping Zhao, Jonna M. Frasor, Yang Dai, Christian Schönbach
2011 PLoS ONE  
Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors, and were highly correlated with a Luminal  ...  The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules and validation studies were carried out in a tamoxifen resistant cell line.  ...  of transcription factors, and a number of small molecules that can reverse expression of genes associated with tamoxifen resistance.  ... 
doi:10.1371/journal.pone.0022274 pmid:21789246 pmcid:PMC3137633 fatcat:fqzzhf4jwveg5kshdh25tyhfye

Genomics-Guided Drawing of Molecular and Pathophysiological Components of Malignant Regulatory Signatures Reveals a Pivotal Role in Human Diseases of Stem Cell-Associated Retroviral Sequences and Functionally-Active hESC Enhancers

Gennadi V. Glinsky
2021 Frontiers in Oncology  
Collectively, reported herein observations support a model of SCARS-activation triggered singular source code facilitating the intracellular propagation and intercellular (systemic) dissemination of disease  ...  These diagnostic and therapeutic approaches are based on monitoring of high-fidelity molecular signals of continuing SCARS activities in conjunction with genomic regulatory networks of thousands' functionally-active  ...  transcription factors, thus, ensuring the transcriptionally-competent chromatin state of defined genomic loci.  ... 
doi:10.3389/fonc.2021.638363 pmid:33869024 pmcid:PMC8044830 fatcat:36mlpaouavc4fdxhkfsrluyrna

Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior

Ee-Lynn Yap, Michael E. Greenberg
2018 Neuron  
In this Review, we provide an overview of the field of activity-dependent transcription in the vertebrate brain and highlight contemporary work that ranges from studies of activity-dependent chromatin  ...  We identify key gaps in knowledge and propose integrated approaches toward a deeper understanding of how activity-dependent transcription promotes the refinement and plasticity of neural circuits for cognitive  ...  ACKNOWLEDGMENTS We apologize to researchers whose work we were not able to cite because of space limitations. We thank Dr. J. Zieg  ... 
doi:10.1016/j.neuron.2018.10.013 pmid:30359600 pmcid:PMC6223657 fatcat:uctnb4gosfgyvjo6pok3ho2r6u

Mechanisms of Oncogene Activation [chapter]

Anca Botezatu, Iulia V. Iancu, Oana Popa, Adriana Plesa, Dana Manda, Irina Huica, Suzana Vladoiu, Gabriela Anton, Corin Badiu
2016 New Aspects in Molecular and Cellular Mechanisms of Human Carcinogenesis  
Among these proteins are transcription factors, chromatin remodelers, growth factors, growth factor receptors, signal transducers, and apoptosis regulators.  ...  the importance of studying oncogenes activation mechanisms and the great potential that they hold as therapeutic tools in the near future.  ...  Acknowledgements This work was supported by Romanian Research Grant PCCA135/2012 and POSDRU/159/1.5 / S/135760  ... 
doi:10.5772/61249 fatcat:rvqp6s7vujgc7a2nk5mksjzim4

Gene Activation by the Cytokine-Driven Transcription Factor STAT1 [chapter]

Roswitha Nast, Julia Staab, Thomas Meyer
2019 Gene Regulation [Working Title]  
Signal transducers and activators of transcription (STATs) are a family of cytokine-regulated transcription factors, which serve the dual role of external signal transduction and transcriptional activation  ...  In particular, we highlight the significance of sequence-specific DNA binding and intact nucleocytoplasmic shuttling for full transcriptional activation of interferon-driven target genes.  ...  The authors gratefully acknowledge the excellent technical assistance of Anke Gregus and Heike Hühn.  ... 
doi:10.5772/intechopen.82699 fatcat:4wtu5yailjfl7bebtn24omntn4

Regulatory activities of transposable elements: from conflicts to benefits

Edward B. Chuong, Nels C. Elde, Cédric Feschotte
2016 Nature reviews genetics  
Transposable elements (TEs) are a prolific source of tightly regulated, biochemically active noncoding elements, such as transcription factor binding sites and non-coding RNAs.  ...  We also discuss the challenges of dissecting and interpreting the phenotypic impact of regulatory activities encoded by TEs in health and disease.  ...  This work was supported by funds from the US National Institutes of Health (GM77582, GM112972, GM059290 to C.F. and GM114514 to N.C.E).  ... 
doi:10.1038/nrg.2016.139 pmid:27867194 pmcid:PMC5498291 fatcat:6kajrylwxvb2bemkzxem5opa7q
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