Departments of Urology and Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Dev Cell. 2011 Sep 13;21(3):575-88. doi: 10.1016/j.devcel.2011.07.003.
Control of gene expression during development requires the concerted action of sequence-specific transcriptional regulators and epigenetic modifiers, which are spatially coordinated within the nucleus through mechanisms that are poorly understood. Here we show that transcriptional repression by the Msx1 homeoprotein in myoblast cells requires the recruitment of Polycomb to target genes located at the nuclear periphery. Target genes repressed by Msx1 display an Msx1-dependent enrichment of Polycomb-directed trimethylation of lysine 27 on histone H3 (H3K27me3). Association of Msx1 with the Polycomb complex is required for repression and regulation of myoblast differentiation. Furthermore, Msx1 promotes a dynamic spatial redistribution of the H3K27me3 repressive mark to the nuclear periphery in myoblast cells and the developing limb in vivo. Our findings illustrate a hitherto unappreciated spatial coordination of transcription factors with the Polycomb complex for appropriate regulation of gene expression programs during development.
在发育过程中控制基因表达需要序列特异性转录调控因子和表观遗传修饰因子的协同作用，这些因子通过机制在核内空间协调，而这些机制尚不清楚。在这里，我们表明，在成肌细胞中，Msx1 同源蛋白的转录抑制需要多梳蛋白募集到位于核周缘的靶基因。Msx1 抑制的靶基因显示出 Msx1 依赖性的组蛋白 H3 赖氨酸 27 上多梳蛋白导向的三甲基化 (H3K27me3) 的富集。Msx1 与多梳复合物的关联对于抑制和调节成肌细胞分化是必需的。此外，Msx1 促进 H3K27me3 抑制标记在成肌细胞和体内发育肢体中的核周缘的动态空间重分布。我们的发现说明了在发育过程中，转录因子与多梳复合物的空间协调对于适当调节基因表达程序的重要性，这是以前未被认识到的。
