Mario Richter

In this work we characterize a novel histone lysine
mono-methyltransferase called Setd6. By enzymatic
assays we demonstrate that this protein is capable
of modifying histone H1, H2A, H3 and H4. For all but
the linker histone H1 we furthermore determine the
exact residue methylated. In mouse NIH 3T3 cells a
reduction of the Setd6 protein level leads to a
misregulation of a set of genes including several
that are important for the regulation of
differentiation and cell line commitment. Amongst
those is a segregated co-regulator of the Wnt
signaling pathway. In immunoprecipitation
experiments we identify specific interactors of
Setd6 in murine immortalized fibroblasts and murine
embryonic stem cells. Again we find proteins that
are important for the Wnt signaling pathway. Taken
together the enzymatic activity and the in cell
results we conclude that we identified a novel
histone lysine mono-methyltransferase possibly
involved in the maintenance of cell line identity
and acting as antagonist of the histone
acetyltransferase Tip60 as both enzymes target the
exact same residues.