Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development

Ten-Eleven Translocation (Tet) family of dioxygenases offers a new mechanism for dynamic regulation of DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functional roles and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further reveal a novel DNA binding mode of the Tet3 CXXC domain that is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are crucial for Tet3’s biological function. Together, these findings define Tet3 as a novel transcription factor and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development

Global, national and local practices in multinational corporations: towards a sociopolitical framework

This paper intends to shed some light on strategies and power resources of subsidiary managers and employee representatives involved in ‘charter changes’ and the implementation of ‘best practices’ developed elsewhere. Research shows that local managers face a dilemma in that they need both internal legitimacy (within the MNC itself) and external legitimacy (within the local context). It is argued that the power resources key actors draw on in the (internal) decision-making processes of ‘charter changes’ are intertwined with certain (external) national business system (NBS) characteristics, an aspect often neglected in North American research about MNCs. The authors identify three key influences, which restrain or empower local management and employees in their ability to make strategic choices and gain power within the MNC. They are (1) the overall strategic approach of the multinational group, (2) the strategic position and the economic performance of the subsidiary itself and (3) the degree of institutional embeddedness of the subsidiary in the host country. Comparative mini-case studies are used to illustrate the effect of local management and employee representatives' empowerment on their ability to retain skills and work practices supportive of a diversified quality production process in the face of MNC pressure to adopt global ‘best practices’ based on more standardized production processes