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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 cellproliferation and differentiation must be precisely coordinated and temporally controlled toensure that a proper number of cells are allocated to various structures. The novel coiled-coilprotein Geminin was previously characterized as a dual function molecule with roles both inmaintenance of genome integrity through regulation of DNA replication licensing and in controlof neural cell fate during embryonic development. However, the mechanistic basis of Geminin'sactivities during embryogenesis and the connections to its cell cycle regulatory role wereunknown. Recently, some of Geminin's activities in regulating transcription were shown tooccur through interactions with Brg1, the catalytic subunit of the SWI/SNF chromatinremodeling complex. During development of the nervous system, Geminin controls thetransition from proliferating precursor to differentiated post-mitotic neuron by modulatinginteractions between SWI/SNF and bHLH transcription factors that are critical for neurogenesis.In other developmental contexts, Geminin mediates proliferative-differentiative transitionsthrough interactions with Six3 and Hox transcription factors and Polycomb Group proteins.Interactions of Geminin with Polycomb and SWI/SNF complex proteins link its transcriptionalactivities to modulation of chromatin structure. Here we incorporate recent findings regardingGeminin's regulatory roles in coordinating proliferation and differentiation duringembryogenesis.