Geminin's double life - Chromatin connections that regulate transcription at the transition from proliferation to differentiation
Geminin's double life - Chromatin connections that regulate transcription at the transition from proliferation to differentiation
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DOI：
10.4161/cc.5.4.2438
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发表时间：
2006-02-15
期刊：
影响因子：
4.3
通讯作者：
Kroll, Kristen L.
中科院分区：
文献类型：
--
作者：
Seo, Seongjin;Kroll, Kristen L.
在胚胎发育过程中，调节祖细胞增殖和分化的细胞程序之间的转换必须精确协调和时间控制，以确保适当数量的细胞分配给各种结构。新的卷曲螺旋蛋白Geminin先前被表征为具有双重功能的分子，其作用是通过调节DNA复制许可来维持基因组完整性，以及在胚胎发育期间控制神经细胞命运。然而，Geminin在胚胎发生过程中的活动机制基础及其与细胞周期调节作用的联系尚不清楚。最近，Geminin的一些活动，在调节转录显示发生通过与Brg 1，催化亚基的SWI/SNF染色质重塑复合物的相互作用。在神经系统发育过程中，Geminin通过调节SWI/SNF和bHLH转录因子之间的相互作用来控制从增殖前体到分化的有丝分裂后神经元的转变，所述转录因子对于神经发生是至关重要的。在其他发育环境中，Geminin通过与Six 3和Hox转录因子和Polycomb Group蛋白的相互作用介导增殖-分化转变。Geminin与Polycomb和SWI/SNF复合蛋白的相互作用将其转录活性与染色质结构的调节联系起来。在这里，我们将最近的研究结果，在协调胚胎发生过程中的增殖和分化的调控作用。
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.