Trimethylation and Acetylation of β-Catenin at Lysine ۴۹ Represent A Key Element in ES Cell Pluripotency

سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 22

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شناسه ملی سند علمی:

SCROYAN14_015

تاریخ نمایه سازی: 14 آبان 1403

چکیده مقاله:

Wnt/β-catenin signaling is required for embryonic stem (ES)cell pluripotency by inducing mesodermal differentiation andinhibiting neuronal differentiation, but how β-catenin counterregulatesthese differentiation pathways is unknown. Here,we show that lysine ۴۹ (K۴۹) of β-catenin is trimethylated(β-catMe۳) by Ezh۲, or acetylated (β-catAc) by Cbp. Significantly,β-catMe۳ acts as a transcriptional co-repressor of theneuronal differentiation genes sox۱ and sox۳, whereas β-catAcacts as a transcriptional co-activator of the key mesodermal differentiationgene t-brachyury (t-bra). Furthermore, β-catMe۳and β-catAc are alternatively enriched on repressed or activatedgenes, respectively, during ES and adult stem cell differentiationinto neuronal or mesodermal progenitor cell lineages. Importantly,expression of a β-catenin K۴۹A mutant results in majordefects in ES cell differentiation. We conclude that β-cateninK۴۹ trimethylation and acetylation are key elements in regulatingES pluripotency and differentiation potential.

نویسندگان

R Kemier

Department of Molecular Embryology, Max-Planck Institute of Immunobiology & Epigenetics, Freiburg, Germany