Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation

Somatic angiotensin-converting enzyme (sACE) is crucial in cardiovascular homeostasis and displays a tissue-specific profile. Epigenetic patterns modulate genes expression and their alterations were implied in pathologies including hypertension. However, the influence of DNA methylation and chromatin condensation state on the expression of sACE is unknown. We examined whether such epigenetic mechanisms could participate in the control of sACE expression in vitro and in vivo. We identified two CpG islands in the human ace-1 gene 3 kb proximal promoter region. Their methylation abolished the luciferase activity of ace-1 promoter/reporter constructs transfected into human liver (HepG2), colon (HT29), microvascular endothelial (HMEC-1) and lung (SUT) cell lines (p < 0.001). Bisulphite sequencing revealed a cell-type specific basal methylation pattern of the ace-1 gene -1,466/+25 region. As assessed by RT-qPCR, inhibition of DNA methylation by 5-aza-2'-deoxycytidine and/or of histone deacetylation by trichostatin A highly stimulated sACE mRNA expression cell-type specifically (p < 0.001 vs. vehicle treated cells). In the rat, in vivo 5-aza-cytidine injections demethylated the ace-1 promoter and increased sACE mRNA expression in the lungs and liver (p = 0.05), but not in the kidney. In conclusion, the expression level of somatic ACE is modulated by CpG-methylation and histone deacetylases inhibition. The basal methylation pattern of the promoter of the ace-1 gene is cell-type specific and correlates to sACE transcription. DNMT inhibition is associated with altered methylation of the ace-1 promoter and a cell-type and tissue-specific increase of sACE mRNA levels. This study indicates a strong influence of epigenetic mechanisms on sACE expression.

Measurement of dijet azimuthal decorrelations in pp collisions at sqrt(s)=7 TeV

Azimuthal decorrelations between the two central jets with the largest transverse momenta are sensitive to the dynamics of events with multiple jets. We present a measurement of the normalized differential cross section based on the full data set (∫Ldt=36  pb(-1)) acquired by the ATLAS detector during the 2010 sqrt(s)=7  TeV proton-proton run of the LHC. The measured distributions include jets with transverse momenta up to 1.3 TeV, probing perturbative QCD in a high-energy regime.

Search for supersymmetry using final states with one lepton, jets, and missing transverse momentum with the ATLAS detector in √s=7 TeV pp collisions

This Letter presents the first search for supersymmetry in final states containing one isolated electron or muon, jets, and missing transverse momentum from √s=7  TeV proton-proton collisions at the LHC. The data were recorded by the ATLAS experiment during 2010 and correspond to a total integrated luminosity of 35  pb(-1). No excess above the standard model background expectation is observed. Limits are set on the parameters of the minimal supergravity framework, extending previous limits. Within this framework, for A(0)=0 GeV, tanβ=3, and μ>0 and for equal squark and gluino masses, gluino masses below 700 GeV are excluded at 95% confidence level.

Search for diphoton events with large missing transverse energy in 7 TeV proton-proton collisions with the ATLAS detector

A search for diphoton events with large missing transverse energy is presented. The data were collected with the ATLAS detector in proton-proton collisions at √s=7 TeV at the CERN Large Hadron Collider and correspond to an integrated luminosity of 3.1 pb⁻¹. No excess of such events is observed above the standard model background prediction. In the context of a specific model with one universal extra dimension with compactification radius R and gravity-induced decays, values of 1/R<729 GeV are excluded at 95% C. L., providing the most sensitive limit on this model to date.

Colon cancer cells produce immunoregulatory glucocorticoids

Expression or release of immunosuppressive molecules may protect tumor cells from the recognition and destruction by the immune system. New findings indicate that colorectal tumors produce immunoregulatory glucocorticoids and thereby suppress immune cell activation. The nuclear receptor LRH-1 plays a critical role in the regulation of colorectal tumor proliferation and glucocorticoid synthesis.