A dynamic and integrated epigenetic program at distal regions orchestrates transcriptional responses to VEGFA.

Cell behaviors are dictated by epigenetic and transcriptional programs. Little is known about how extracellular stimuli modulate these programs to reshape gene expression and control cell behavioral responses. Here, we interrogated the epigenetic and transcriptional response of endothelial cells to VEGFA treatment and found rapid chromatin changes that mediate broad transcriptomic alterations. VEGFA-responsive genes were associated with active promoters, but changes in promoter histone marks were not tightly linked to gene expression changes. VEGFA altered transcription factor occupancy and the distal epigenetic landscape, which profoundly contributed to VEGFA-dependent changes in gene expression. Integration of gene expression, dynamic enhancer, and transcription factor occupancy changes induced by VEGFA yielded a VEGFA-regulated transcriptional regulatory network, which revealed that the small MAF transcription factors are master regulators of the VEGFA transcriptional program and angiogenesis. Collectively these results revealed that extracellular stimuli rapidly reconfigure the chromatin landscape to coordinately regulate biological responses.

An experimental study of a modified dahuang zhechong pill on the--angiogenesis of RF/6A cells in vitro.

OBJECTIVE: To investigate the effects of a modified Dahuang Zhechong Pill (MDZP) on the angiogenesis of rhesus choroid-retina endothelial (RF/6A) cells and its preliminary mechanism. METHODS: A 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) method was used to assess the effect of a MDZP on RF/6A cell proliferation induced by vascular endothelial growth factor (VEGF). Transwell inserts were used to assess the effect of the MDZP on RF/6A cell migration. Matrigel was used to assess the effect of the MDZP on the tube formation of RF/ 6A cells. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) were used to detect the protein and mRNA expression, respectively, of VEGF and matrix metalloproteinase-2 (MMP-2) in RF/6A cells treated with the MDZP. RESULTS: RF/6A cell proliferation induced by VEGF was inhibited by 0.2 mg/mL MDZP. At 0, 12.5, 25 and 50 mg/mL MDZP, the number of cells that migrated through Transwell membranes was 73.33 +/- 4.51, 61.33 +/- 4.04, 28.67 +/- 6.66 and 17.67 +/- 4.16, respectively, and the number of tubes formed in Matrigel was 20.33 +/- 0.58, 13.33 +/- 1.53, 11.00 +/- 1.00 and 1.33 +/- 0.58, respectively. At 100 and 200 mg/mL MDZP, the protein and mRNA expression of VEGF and MMP-2 were inhibited in RF/6A cells. At 400 mg/mL MDZP, the expression of VEGF mRNA and MMP-2 protein were inhibited in RF/6A cells. CONCLUSIONS: MDZP inhibits the angiogenesis of RF/6A cells via the suppression of proliferation, migration and tube formation of RF/6A cells. Inhibition of the protein and mRNA expression of VEGF and MMP-2 in RF/6A cells may be an important mechanism.

Green light extends Drosophila longevity.

The role of visible light on longevity is incompletely understood. Here we show the effect of visible light in Drosophila melanogaster is wavelength specific. Life span was significantly extended by green light, whereas blue light reduced longevity dramatically, and minor impact was observed with red light. While oxidative stress, heat stress, or caloric restriction does not contribute to the beneficial effect of green light, our study found that the life span extension effect of green light might be mediated by microbiota or photosensitive micronutrients in food medium. In conclusion, we report that green light can extend longevity and present the potential of light as a noninvasive therapy for aging-related diseases.