Geminin's double life: Chromatin connections that regulate transcription at the transition from proliferation to differentiation

During embryonic development, transitions between cellular programs regulating progenitor cell proliferation and differentiation must be precisely coordinated and temporally controlled to ensure that a proper number of cells are allocated to various structures. The novel coiled-coil protein Geminin was previously characterized as a dual function molecule with roles both in maintenance of genome integrity through regulation of DNA replication licensing and in control of neural cell fate during embryonic development. However, the mechanistic basis of Geminin's activities during embryogenesis and the connections to its cell cycle regulatory role were unknown. Recently, some of Geminin's activities in regulating transcription were shown to occur through interactions with Brg1, the catalytic subunit of the SWI/SNF chromatin-remodeling complex. During development of the nervous system, Geminin controls the transition from proliferating precursor to differentiated post-mitotic neuron by modulating interactions between SWI/SNF and bHLH transcription factors that are critical for neurogenesis. In other developmental contexts, Geminin mediates proliferative-differentiative transitions through interactions with Six3 and Hox transcription factors and Polycomb Group proteins. Interactions of Geminin with Polycomb and SWI/SNF complex proteins link its transcriptional activities to modulation of chromatin structure. Here we incorporate recent findings regarding Geminin's regulatory roles in coordinating proliferation and differentiation during embryogenesis.