J 2015

CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli

FRANEK, Michal; Soňa LEGARTOVÁ; Jana SUCHÁNKOVÁ; C MILITE; S CASTELLANO et al.

Základní údaje

Originální název

CARM1 Modulators Affect Epigenome of Stem Cells and Change Morphology of Nucleoli

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Vydání

Physiological Research, Praha, Fyziologický ústav AV ČR, 2015, 0862-8408

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 1.643

Označené pro přenos do RIV

Ne

Klíčová slova anglicky

Epi-drugs; Histones; Epigenetics; ES cells; iPS cells; Nucleoli
Změněno: 6. 10. 2016 10:28, Mgr. Jana Suchánková, Ph.D.

Anotace

V originále

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.