Histone modifying enzymes play critical roles in cell differentiation and development. In this study, we report that SMYD2 (SET and MYND domain containing protein 2), a histone lysine methyltransferase, is induced during human embryonic stem (ES) cell differentiation and it is preferentially expressed in somatic cells versus pluripotent cells. Knockdown of SMYD2 in human ES cells promotes the induction of endodermal markers during differentiation, while overexpression has opposite effects. In vivo experiments in zebrafish revealed that knockdown of smyd2a (a homologue gene of human SMYD2) causes developmental delay and aberrant tail formation, which is coincident with low expression of ntl and over induction Nodal-related genes during gastrulation. Taken together, these findings suggest that SMYD2 plays a critical role at early stages of development and in human ES cell differentiation.
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