These findings suggest that Th17-related cytokines can contribute to recall-like expansion and effector function of Ag-specific gamma delta T cells after infection or vaccination.”
“Hypoxia-inducible factor 1 (HIF-1) emerges as a crucial player in tumor progression. However, its role in hepatocellular carcinoma (HCC), especially its relation with global DNA methylation MK-2206 PI3K/Akt/mTOR inhibitor patterns in HCC under hypoxic tumor microenvironment is not completely understood. Methionine adenosyltransferase 2A (MAT2A) maintains the homeostasis

of S-adenosylmethionine (SAM), a critical marker of genomic methylation status. In this study, we investigated the link between HIF-1 alpha and MAT2A as a mechanism responsible for the change in genomic DNA methylation patterns in liver cancer under hypoxia conditions. Our results showed that hypoxia induces genomic DNA demethylation in CpG islands by reducing the steady-state SAM level both in vitro and in vivo. In addition, HIF-1 alpha and MAT2A expression is correlated with tumor size and TNM stage of liver cancer tissues. We further showed that hypoxia-induced MAT2A expression is HIF-1 alpha dependent and requires the recruitment of p300 and HDAC1.

We also identified an authentic consensus HIF-1 alpha binding site in MAT2A promoter by site-directed mutagenesis, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay. Taken together, we show for the first time that hypoxia induces genomic DNA demethylation through the activation of HIF-1 alpha and transcriptional upregulation of MAT2A in hepatoma cells. These 4SC-202 findings provide new

insights into our understanding of the molecular link between genomic DNA methylation and tumor hypoxia in HCC. Mol Cancer Ther; 10(6); 1113-23. (C)2011 AACR.”
“HpdR, an IcIR-family regulator in Streptomyces coelicolor, is a substrate-dependent repressor for the tyrosine catabolic gene hppD. In this study, Si nuclease protection assays revealed that hpdR is subject to a negative autoregulation. Purified HpdR showed specific 10058-F4 mouse DNA-binding activity for the promoter region of hpdR, indicating that the autoregulation of hpdR is performed directly. The disruption of hpdR led to reduced production of CDA by S. coelicolor J1501, suggesting a positive effect of hpdR on CDA biosynthesis. Electrophoretic mobility shift assays showed that HpdR specifically bound to the promoter region of hmaS (SCO3229 in the CDA gene cluster), encoding 4-hydroxymandelic acid synthase. Disruption of hmaS in 11501 abolished CDA production. It is possible that hpdR regulates CDA biosynthesis by controlling the transcription of hmaS.”
“Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple.