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E-GEOD-33162 - HDAC3 requirement for the inflammatory gene expression program in macrophages [gene expression]

Status
Released on 8 July 2012, last updated on 17 July 2012
Organism
Mus musculus
Samples (12)
Array (1)
Protocols (8)
Description
Pan-Hdac inhibitors (HDACi) are endowed with a potent anti-inflammatory activity, but the relative role of each of the eleven Hdac proteins sensitive to HDACi to the inflammatory gene expression program is unknown. Using an integrated genomic approach we found that Hdac3-deficient macrophages are unable to activate almost half of the inflammatory gene expression program when stimulated with lipopolysaccharide (LPS). A large part of the activation defect is due to loss of basal and LPS-inducible expression of IFNb, which in basal cells maintains Stat1 protein levels, and after stimulation acts in an autocrine/paracrine manner to promote a secondary wave of Stat1-dependent gene expression. We show that loss of Hdac3-mediated repression of nuclear receptors leads to hyperacetylation of thousands of genomic sites and associated gene derepression. The upregulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), has a causative role in the phenotype, since its chemical inhibition reverts the Ifnb activation defect. These data may have relevance for the use of selective Hdac inhibitors as anti-inflammatory agents. Gene expression profiles for bone marrow-derived macrophages from either HDAC3 +/- (wt) or HDAC3 -/- (KO). Cells were left untreated or challenged with lipopolysaccharide (LPS) for 4hrs. Each genotype-treatment combination was performed in triplicate.
Experiment type
transcription profiling by array 
Contacts
Iros Giacomo Barozzi <giacomo.barozzi@ifom-ieo-campus.it>, Alberto Termanini, Elena Prosperini, Flore Mietton, Gianluca Matteoli, Gioacchino Natoli, Iros Barozzi, Scott Hiebert, Xuefen Chen
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-33162.idf.txt
Sample and data relationshipE-GEOD-33162.sdrf.txt
Raw data (1)E-GEOD-33162.raw.1.zip
Processed data (1)E-GEOD-33162.processed.1.zip
Array designA-AFFY-130.adf.txt
R ExpressionSetE-GEOD-33162.eSet.r
Links