A major goal in efforts to understand the mechanisms by which signal transduction pathways regulate programs of gene expression is to identify their direct target genes and to determine the specific components of the transcriptional machinery that are recruited to these genes in response to regulatory signals. To support these goals, the Transcriptional Genomics Core will provide three complementary services to PPG investigators;conventional gene expression (Chip) microarray analysis, recently developed genomic (ChIPChip) microarray analysis, and associated Bioinformatics support for experimental design oversight and data analysis. Conventional expression analysis will utilize commercially available microarrays (e.g., Affymetrix, Agilent and Illumina microarrays). Recent progress in combining the use of chromatin immunoprecipitation (ChIP) assays with DMA microarrays has allowed genome-wide analysis of transcription factor localization to specific promoter sequences in living cells. The PPG Transcriptional Genomics Core will fabricate murine intergenic/promoter microarrays to allow genome-wide location analysis of PPARs, NCoR, SMRT, and other transcription factors of relevance to this application. Effective utilization of genome-wide approaches requires an understanding of the strengths and limitations of these technologies, particularly with respect to sources of error and the number of experimental replicates that are required to develop gene lists at defined and acceptable false positive and false negative rates. Personnel within the PPG Transcriptional Genomics Core will interact with scientists within each of the Projects to provide experimental design oversight focused on these issues. Once microarray experiments are performed and raw data is collected, the Transcriptional Genomics Core will utilize standard tools to develop gene lists at specified levels of confidence and perform secondary analysis (e.g., Gene Ontology analysis, mapping to KEGG pathways, etc.). The Transcriptional Genomics Core will provide a database infrastructure for data storage and retrieval to allow integration of data collected across the PPG and the application of more sophisticated bioinformatics approaches outlined in each of the Projects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL088093-05
Application #
8375398
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$178,756
Indirect Cost
$63,394
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Sherman, Mara H; Yu, Ruth T; Tseng, Tiffany W et al. (2017) Stromal cues regulate the pancreatic cancer epigenome and metabolome. Proc Natl Acad Sci U S A 114:1129-1134
Fan, Weiwei; Evans, Ronald M (2017) Exercise Mimetics: Impact on Health and Performance. Cell Metab 25:242-247
Choi, Soo-Ho; Sviridov, Dmitri; Miller, Yury I (2017) Oxidized cholesteryl esters and inflammation. Biochim Biophys Acta 1862:393-397
He, Nanhai; Fan, Weiwei; Henriquez, Brian et al. (2017) Metabolic control of regulatory T cell (Treg) survival and function by Lkb1. Proc Natl Acad Sci U S A 114:12542-12547
Shalapour, Shabnam; Lin, Xue-Jia; Bastian, Ingmar N et al. (2017) Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature 551:340-345
van Capelleveen, Julian C; Bernelot Moens, Sophie J; Yang, Xiaohong et al. (2017) Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study. Arterioscler Thromb Vasc Biol 37:1206-1212
Fan, Weiwei; Waizenegger, Wanda; Lin, Chun Shi et al. (2017) PPAR? Promotes Running Endurance by Preserving Glucose. Cell Metab 25:1186-1193.e4
Doktorova, Marcela; Zwarts, Irene; Zutphen, Tim van et al. (2017) Intestinal PPAR? protects against diet-induced obesity, insulin resistance and dyslipidemia. Sci Rep 7:846
Wang, Jianrong; He, Nanhai; Zhang, Na et al. (2017) NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection. Nat Commun 8:959
Liu, Chao; Gaudet, Daniel; Miller, Yury I (2017) Deficient Cholesterol Esterification in Plasma of apoc2 Knockout Zebrafish and Familial Chylomicronemia Patients. PLoS One 12:e0169939

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