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Fig. 8 | Epigenetics & Chromatin

Fig. 8

From: Nucleophosmin 1 cooperates with the methyltransferase DOT1L to preserve peri-nucleolar heterochromatin organization by regulating H3K27me3 levels and DNA repeats expression

Fig. 8

Cartoon model of NPM1 and DOT1L functions in regulating their expression and in heterochromatin organization around the nucleoli. Left: WT situation in which NPM1 restricts DOT1L expression levels and DOT1L promotes NPM1 expression. Moderate expression of DNA repeats in peri-nucleolar heterochromatin is accompanied with moderate levels of H3K27me3, mediated by the PRC2 member EZH2. Nucleoli integrity and peri-nucleolar heterochromatin is preserved by expression of NPM1. Right: NPM1 KD leads to increased levels of DOT1L expression and H3K79me2. Both, NPM1 and DOT1L regulate Ezh2 transcription, whereby its levels depend on DOT1L concentrations. NPM1 KD alike DOT1L OE increase H3K79me2 and H3K27me3 levels at DNA repeats and repress basic expression of the DNA repeats. In addition to silencing of the DNA repeats in the peri-nucleolar heterochromatin through an altered epigenome, the structure of the heterochromatin and of the nucleoli is also affected towards larger DNA repeat foci and fragmented nucleoli

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Epigenetics & Chromatin

ISSN: 1756-8935