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The enigma of histone 3 lysine 4 methylation

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All active eukaryotic promoters are characterised by nucleosomes that are trimethylated on histone 3 lysine 4 (H3K4me3) and most mammalian enhancers display H3K4me1. Consequently current dogma contends that H3K4 methyltransferases operate as co-factors in transcriptional activation. Functional scrutiny does not sustain this dogma. In yeast, which has only one H3K4 methyltransferase – Set1C, originally described by my lab and also called COMPASS , loss of Set1C counterintuitively promotes more increased gene expression than reduced. In mammals, the six H3K4 methyltransferases have very specific, not general, functions in mouse development.

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