Previous ARMI Wednesday seminars
Prof Francis Stewart
Date: 3rd March 2010
Time: 10:00am - 11:00am
Location: MISCL Seminar Room, 3rd floor, building 75, Clayton campus
Prof Francis Stewart
Professor of Genomics
BioInnovaDonsZentrum,
Technische Universitaet Dresden (TUD), Germany EpigeneDc aspects of acDve chromaDn; MLL and histone 3 lysine
4 methylaDon in mammalian development
Lysine methylaDon of histone 3 is the cornerstone of epigeneDc regulaDon. We are studying this
process in yeast and mice with a focus on methylaDon of lysine 4 (H3K4me), which is the
defining mark for acDve chromaDn. In parDcular trimethylaDon H3K4 is a characterisDc of
nucleosomes at promoters. Whereas yeast has only one enzyme, Set1, that methylates H3K4,
mammals have at least six, including Mll (mixed lineage leukemia), which is the orthologue of
fly Trithorax. Recently we have uncovered evidence that these six enzymes control different
lineages and processes. In parDcular Mll2 appears to be specifically required for the neural
lineage whereas Mll relates to the mesodermal lineage. Mll2 is also required for both
spermatogenesis and oogenesis, although for different reasons. Notably neither Mll or Mll2 are
required to sustain pluripotency, however the mammalian Set1 appears to carry this role.
Hence the mammalian H3K4 methyltransferases appear to regulate different gene expression
programs, which adds an unexpected new dimension to transcripDonal control.
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