Abstract
BackgroundPluripotent cells maintain a unique gene expression pattern and specific chromatin signature. In this study, we explored the effect of the methyltransferase inhibitor adenosine dialdehyde (AdOx) on pluripotency maintenance and gene expression in P19 embryonal carcinoma cells.ResultsAfter AdOx treatment, the pluripotency-related gene network became disordered, and the early developmental genes were released from the repression. Remarkably, AdOx caused contrasting effects on the expression of two key pluripotency genes, nanog and oct3/4, with the reduction of the repressive histone marks H3K27me3, H3K9me3 and H3K9me2 only in the nanog gene.ConclusionsKey pluripotency genes were controlled by different mechanisms, including the differential enrichment of repressive histone methylation marks. These data provided novel clues regarding the critical role of histone methylation in the maintenance of pluripotency and the determination of cell fate in P19 pluripotent cells.
Highlights
Pluripotent cells maintain a unique gene expression pattern and specific chromatin signature
AdOx reduces the neuronal lineage potential of P19 cells To explore whether AdOx affects the maintenance of pluripotency, we examined the neuronal differentiation potential of AdOx-treated P19 cells
We found that the retinoic acid (RA)-induced expression of these early neuronal transcription factors was remarkably reduced or completely abolished at the mRNA level in the presence of AdOx (Figure 1G)
Summary
Pluripotent cells maintain a unique gene expression pattern and specific chromatin signature. Consistent with the wide array of developmental fates, the chromatin in pluripotent cells is highly adaptable [3]. The unique gene expression pattern and chromatin signature in pluripotent cells are controlled by a transcription factor network that involves Oct3/4, Sox, and Nanog [1]. These three core factors are tightly regulated, and even limited fluctuation in their expression may cause significant changes in cell fate [4,5]. In ES cells, the pluripotency-related genes have relatively high levels of the active histone mark H3K4me in their chromatin. The chromatin that contains poised developmental genes is associated with a combination of H3K4me and repressive
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