The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
JAK2 phosphorylates histone H3Y41 and excludes HP1α from chromatin
Open accessAbstract
Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies. 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 1α (HP1α), but not HP1β, 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 HP1α at the same site. These 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 leukaemia.
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Cites
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883
Self-citationAcquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
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Self-citationA unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera
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A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
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Self-citationMethylation of histone H3 lysine 9 creates a binding site for HP1 proteins
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The CBP co-activator is a histone acetyltransferase
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JAK2 Exon 12 Mutations in Polycythemia Vera and Idiopathic Erythrocytosis
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Cited by
Regulation of chromatin by histone modifications
Bannister, A. J., & Kouzarides, T. (2011) · Cell Research · doi:10.1038/cr.2011.22 · Cited by 6,012
Self-citationCancer epigenetics: from mechanism to therapy
Dawson, M. A., & Kouzarides, T. (2012) · Cell · doi:10.1016/j.cell.2012.06.013 · Cited by 3,203
Self-citationRevisiting STAT3 signalling in cancer: new and unexpected biological functions
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3818 · Cited by 2,137
Cancer epigenetics reaches mainstream oncology
Rodríguez-Paredes, M., & Esteller, M. (2011) · Nature Medicine · doi:10.1038/nm.2305 · Cited by 1,205
JAKs and STATs in immunity, immunodeficiency, and cancer
O'Shea, J. J., Holland, S. M., & Staudt, L. M. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1202117 · Cited by 927
Metadata
- Authors
- Dawson, M. A., Bannister, A. J., Göttgens, B., Foster, S. D., Bartke, T., Green, A. R., & Kouzarides, T.
- Venue
- Nature
- Published
- 2009-09-27
- Volume
- 461
- Issue
- 7265
- Pages
- 819-822
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2051181798
- Cited by
- 622
- References
- 42
- FWCI
- 23.16
- Type
- journal article
- Language
- en
- Open access
- green
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