CARM1 i nteracts with numerous transcription factors to mediate cellular processes, especially gene expression. This is important for the maintenance of ESC pluripotency or intervention to tumorigenesis. Here, we studied epigenomic effects of two potential CARM1 m odulators: an activator (EML159) and an inhibitor (ellagic acid dihydrate, EA). We examined nuclear morphology in human and mouse embryonic stem cells (hESCs, mESCs), as well as in iPS cells. The CARM1 modulators did not function similarly in all cell type s. EA decreased the levels of the pluripotency markers, OCT4 and NANOG, particularly in iPSCs, whereas the levels of these proteins increased after EML159 treatment. EML159 treatment of mouse ESCs led to decreased levels of OCT4 and NANOG, which was accomp anied by an increased level of Endo -A. The same trend was observed for NANOG and Endo -A in hESCs affected by EML159. Interestingly, EA mainly changed epigenetic features of nucleoli because a high level of arginine asymmetric di- methylation in the nucleoli of hESCs was reduced after EA treatment. ChIP -PCR of ribosomal genes confirmed significantly reduced levels of H3R17me2a, in both the promoter region of ribosomal genes and rDNA encoding 28S rRNA, after EA addition. Moreover, EA treatment changed the nuclear pattern of AgNORs (silver -stained nucleolus organizer regions) in all cell types studied. In EA -treated ESCs, AgNOR pattern was similar to the pattern of AgNORs after inhibition of RNA pol I by actinomycin D. Together, inhibitory effect of EA on arginine methylation and effect on related morphological parameters was especially observed in compartment of nucleoli., M. Franek, S. Legartová, J. Suchánková, C. Milite, S. Castellano, G. Sbardella, S. Kozubek, E. Bártová., and Obsahuje bibliografii
The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental fac tors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factor s but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics., J. Kuneš, I. Vaněčková, B. Mikulášková, M. Behuliak, L. Maletínská, J. Zicha., and Obsahuje bibliografii