Molecular Biology

Silencing miRNAs

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Science  15 Aug 2008:
Vol. 321, Issue 5891, pp. 893
DOI: 10.1126/science.321.5891.893a

In embryonic stem cells, the genes that specify differentiated cells are silenced. The extent of regulation of microRNAs (miRNAs), which also contribute to tissue differentiation, has been unclear because of the difficulty in locating their promoters. Marson et al. have identified the promoters, using a tell-tale trimethylated histone, on the human and mouse genomes in embryonic stem cells and also in precursor neurons and embryonic fibroblasts. In stem cells, some miRNA promoters were occupied by the four transcription factors (Oct4/Sox2/Nanog/Tcf2) that confer embryonic cell pluripotency, and many of the miRNAs were actively transcribed. In contrast, a subset of these miRNA promoters was occupied by Polycomb group proteins, which are known to silence expression, and these Polycomb-bound miRNA genes were specifically induced in the neural precursors and the fibroblast cells. Therefore, like protein-encoding genes, miRNA genes that drive differentiation are repressed in embryonic stem cells. — KK

Cell 134, 521 (2008).

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