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CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli
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SYSNO ASEP 0472043 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli Author(s) Franek, Michal (BFU-R)
Legartová, Soňa (BFU-R) ORCID
Suchánková, Jana (BFU-R)
Milite, C. (IT)
Castellano, S. (IT)
Sbardella, G. (IT)
Kozubek, Stanislav (BFU-R) RID
Bártová, Eva (BFU-R) ORCIDNumber of authors 8 Source Title Physiological Research. - : Fyziologický ústav AV ČR, v. v. i. - ISSN 0862-8408
Roč. 64, č. 5 (2015), s. 769-782Number of pages 14 s. Publication form Print - P Language eng - English Country CZ - Czech Republic Keywords arginine methyltransferase 1 ; histone deacetylase inhibitors ; gene-expression ; pyrazole inhibitors Subject RIV BO - Biophysics R&D Projects GAP302/10/1022 GA ČR - Czech Science Foundation (CSF) GBP302/12/G157 GA ČR - Czech Science Foundation (CSF) GA13-07822S GA ČR - Czech Science Foundation (CSF) Institutional support BFU-R - RVO:68081707 UT WOS 000367154800019 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2017
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