r.l. All rights reserved.”
“As a ligand-dependent transcription factor of the nuclear hormone receptor superfamily, the pregnane X receptor (PXR) has a multitude of functions including regulating xenobiotic and cholesterol metabolism, energy homeostasis, gut mucosal defense, and cancer development. Whereas the detoxification functions of PXR have been widely studied and well established, the role of PXR in cancer has become controversial. With more than 60% of non-prescription and prescription drugs being metabolized by cytochrome P450 enzyme 3A4 selleck screening library (CYP3A4), a transcriptional

target of PXR, insights into the regulation of PXR during systemic administration of novel treatment modalities will lead to a better understanding of PXR function in the context of human disease. Previous studies have

suggested that PXR activation decreases drug sensitivity and augments chemoresistance in certain colon cancers mainly through the upregulation of CYP3A4 and multidrug resistance protein-1 (MDR1). Later studies suggest that downregulation of PXR expression may be oncogenic in hormone-dependent breast and endometrial cancers by reducing estrogen metabolism via CYP3A4; thus, higher estradiol concentrations contribute to carcinogenesis. These results suggest a differential role of PXR in tumor growth P005091 regulation dependent on tissue type and tumor microenvironment. Here, we will summarize the various mechanisms utilized by PXR to induce its diverse effects on cancerous tissues. Moreover, current approaches will be explored to evaluate the exploitation of PXR-mediated pathways as a novel mechanistic approach to FK506 mw cancer therapy.”
“The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding

gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.