Trimethylation and Acetylation of ß-Catenin at Lysine 49 Represent Key Elements 
in ESC Pluripotency

Hoffmeyer, Katrin; Junghans, Dirk; Kanzler, Benoit; Kemler, Rolf

doi:10.1016/j.celrep.2017.02.076

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Trimethylation and Acetylation of ß-Catenin at Lysine 49 Represent Key Elements in ESC Pluripotency

MPG-Autoren

Hoffmeyer, Katrin
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kanzler, Benoit
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kemler, Rolf
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Zitation

Hoffmeyer, K., Junghans, D., Kanzler, B., & Kemler, R. (2017). Trimethylation and Acetylation of ß-Catenin at Lysine 49 Represent Key Elements in ESC Pluripotency. Cell Reports, 18, 2815-2824. doi:10.1016/j.celrep.2017.02.076.

Zitierlink: https://hdl.handle.net/11858/00-001M-0000-002E-85FA-6

Zusammenfassung

Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra). Furthermore, β-catMe3 and β-catAc are alternatively enriched on repressed or activated genes, respectively, during ESC and adult stem cell differentiation into neuronal or mesodermal progenitor cell lineages. Importantly, expression of a β-catenin K49A mutant results in major defects in ESC differentiation. We conclude that β-catenin K49 trimethylation and acetylation are key elements in regulating ESC pluripotency and differentiation potential.