2009.10.08 – JAK2 phosphorylates histone H3Y41 and excludes HP1 from chromatin


JAK2 phosphorylates histone H3Y41 and excludes HP1 from chromatin

Nature 461(7265):819 (2009)
Mark A Dawson, Andrew J Bannister, Berthold Göttgens, Samuel D Foster, Till Bartke, Anthony R Green and Tony Kouzarides

Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies1, 2, 3, 4, 5, 6. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signalling cascades. Here we show that human JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates Tyr 41 (Y41) on histone H3. Heterochromatin protein 1 (HP1), but not HP1, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukaemic cells decreases both the expression of the haematopoietic oncogene lmo2 and the phosphorylation of H3Y41 at its promoter, while simultaneously increasing the binding of HP1 at the same site. &Tgr;hese results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, jak2 and lmo2, involved in normal haematopoiesis and leukaemia1, 2, 3, 4, 5, 6, 7, 8, 9. DOI: 10.1038/nature08448