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Series GSE20088 Query DataSets for GSE20088
Status Public on Jan 29, 2010
Title Profiling of genes deregulated in CD4+ T cells expressing constitutively full-length or first-exon Tat protein of HIV-1
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background: The role of HIV-1 Tat protein in gene expression deregulation and functional biology of CD4+ T lymphocytes was analyzed, as well as the function of Tat second exon for the complete activity of this protein. Gene expression deregulation profiles of triplicate samples from Jurkat cells expressing intracellular full-length Tat (1-101aa) in comparison with a truncated form lacking the second exon (1-72aa) was evaluated by bioinformatics using whole human genome microarrays. Results: More than 1000 genes were deregulated in Jurkat Tat101 cells, whereas less than 300 genes were deregulated in Jurkat Tat72 cells (q-value<5%; fold change >2 or <-2). Ontological analysis indicated that several functions were impaired mainly in Jurkat Tat101 as cellular movement, growth and proliferation, cell-to-cell signaling, molecular transport, cell death, cell morphology, and T-cell activation. In accordance, biological and functional analyses proved that Tat101 intracellular expression induced changes in cell size and complexity, cytoskeletal rearrangements and chemotaxis impairment, higher resistance to apoptosis, decrease in the surface expression of adhesion molecules and receptors, and higher basal transcriptional activation. These alterations were attenuated or absent in Jurkat Tat72 cells. Furthermore, computational modeling showed that the absence of second exon severely reduced the C-terminus of Tat72 with notable decrease of positive charging. Conclusion: Full-length Tat intracellular expression induced dramatic structural changes and impaired essential functions in CD4+ T cells, whereas Tat72 was less aggressive. Consequently, although Tat first exon is transcriptionally autonomous, second exon should be indispensable for triggering HIV-1 pathogenic events induced by Tat protein.

Keywords: Microarray Genome-wide expression analysis. Comparison of genetically modified cells
 
Overall design Total RNA was obtained from Jurkat cell lines that express constitutively intracellular HIV-1 Tat101 or Tat72. Gene expression profiles were obtained for each sample and compared with a parental Jurkat cell line that does not express Tat.
 
Contributor(s) López-Huertas M, Callejas S, Abia D, Dopazo A, Alcamí J, Coiras M
Citation(s) 20139419
Submission date Jan 28, 2010
Last update date Jan 23, 2019
Contact name Sergio Callejas
Organization name Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Department Genomics Unit
Lab Genomics Unit
Street address Melchor Fernández Almagro, 3
City Madrid
ZIP/Postal code 28029
Country Spain
 
Platforms (1)
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
Samples (9)
GSM502007 Jurkat-TetOff-rep1
GSM502008 Jurkat-Exon1-rep1
GSM502009 Jurkat-complete-rep1
Relations
BioProject PRJNA124289

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE20088_RAW.tar 47.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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