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@article{1356018,
author = {Franek, Michal and Legartová, Soňa and Suchánková, Jana and Milite, C and Castellano, S and Sbardella, G and Kozubek, Stanislav and Bártová, Eva},
article_location = {Praha},
article_number = {5},
keywords = {Epi-drugs; Histones; Epigenetics; ES cells; iPS cells; Nucleoli},
language = {eng},
issn = {0862-8408},
journal = {Physiological Research},
title = {CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli},
volume = {64},
year = {2015}
}
TY - JOUR
ID - 1356018
AU - Franek, Michal - Legartová, Soňa - Suchánková, Jana - Milite, C - Castellano, S - Sbardella, G - Kozubek, Stanislav - Bártová, Eva
PY - 2015
TI - CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli
JF - Physiological Research
VL - 64
IS - 5
SP - 769-782
EP - 769-782
PB - Fyziologický ústav AV ČR
SN - 08628408
KW - Epi-drugs
KW - Histones
KW - Epigenetics
KW - ES cells
KW - iPS cells
KW - Nucleoli
N2 - CARM1 interacts 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 modulators: 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 types. 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 accompanied 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.
ER -
FRANEK, Michal, Soňa LEGARTOVÁ, Jana SUCHÁNKOVÁ, C MILITE, S CASTELLANO, G SBARDELLA, Stanislav KOZUBEK a Eva BÁRTOVÁ. CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli. \textit{Physiological Research}. Praha: Fyziologický ústav AV ČR, 2015, roč.~64, č.~5, s.~769-782. ISSN~0862-8408.
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