Protein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1 methyltransferase complex and contributes to the regulation of multiple target genes
Wiersma M, Bussiere M, Halsall JA, Turan N, Slany R, Turner BM, Nightingale KP (2016)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2016
Journal
Publisher: BioMed Central Ltd.
Book Volume: 9
Pages Range: 1-12
Journal Issue: 1
DOI: 10.1186/s13072-016-0103-3
Abstract
Background: The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear. Results: KMT2A/MLL1 (both native and FLAG-tagged) and Msk1 (RPS6KA5) co-immunoprecipitated in various cell types. KMT2A/MLL1 and Msk1 knockdown demonstrated that the great majority of genes whose activity changed on KTM2A/MLL1 knockdown, responded comparably to Msk1 knockdown, as did levels of H3K4 methylation and H3S10 phosphorylation at KTM2A target genes HoxA4, HoxA5. Knockdown experiments also showed that KMT2A/MLL1 is required for the genomic targeting of Msk1, but not vice versa. Conclusion: The KMT2A/MLL1 complex is associated with, and functionally dependent upon, the kinase Msk1, part of the MAP kinase signalling pathway. We propose that Msk1-catalysed phosphorylation at H3 serines 10 and 28, supports H3K4 methylation by the KMT2A/MLL1 complex both by making H3 a more attractive substrate for its SET domain, and improving target gene accessibility by prevention of HP1- and Polycomb-mediated chromatin condensation.
Authors with CRIS profile
Involved external institutions
United Kingdom (GB)How to cite
APA:
Wiersma, M., Bussiere, M., Halsall, J.A., Turan, N., Slany, R., Turner, B.M., & Nightingale, K.P. (2016). Protein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1 methyltransferase complex and contributes to the regulation of multiple target genes. Epigenetics & Chromatin, 9(1), 1-12. https://doi.org/10.1186/s13072-016-0103-3
MLA:
Wiersma, Maaike, et al. "Protein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1 methyltransferase complex and contributes to the regulation of multiple target genes." Epigenetics & Chromatin 9.1 (2016): 1-12.
BibTeX: Download