Sesé Borja, Barrero Maria J, Fabregat Maria-Carme, Sander Veronika, Izpisua Belmonte Juan Carlos
Center for Regenerative Medicine in Barcelona, Barcelona, Spain.
Int J Dev Biol. 2013;57(5):357-64. doi: 10.1387/ijdb.130051ji.
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.
组蛋白修饰酶在细胞分化和发育中起着关键作用。在本研究中,我们报道了SMYD2(含SET和MYND结构域蛋白2),一种组蛋白赖氨酸甲基转移酶,在人类胚胎干细胞(ES细胞)分化过程中被诱导,并且它在体细胞中相对于多能细胞优先表达。在人类ES细胞中敲低SMYD2可促进分化过程中内胚层标志物的诱导,而过度表达则具有相反的作用。斑马鱼体内实验表明,敲低smyd2a(人类SMYD2的同源基因)会导致发育延迟和异常的尾巴形成,这与原肠胚形成过程中ntl的低表达和Nodal相关基因的过度诱导相一致。综上所述,这些发现表明SMYD2在发育早期和人类ES细胞分化中起着关键作用。