de la Cruz Cecile C, Fang Jia, Plath Kathrin, Worringer Kathleen A, Nusinow Dmitri A, Zhang Yi, Panning Barbara
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Chromosoma. 2005 Aug;114(3):183-92. doi: 10.1007/s00412-005-0008-6. Epub 2005 Jun 29.
Chromatin modifications are among the epigenetic alterations essential for genetic reprogramming during development. The Polycomb group (PcG) gene family mediates chromatin modifications that contribute to developmentally regulated transcriptional silencing. Trimethylation of histone H3 on lysine 27, mediated by a PcG protein complex consisting of Eed, Ezh2, and Suz12, is integral in differentiation, stem cell self-renewal, and tumorigenesis. Eed and Ezh2 are also implicated in the developmentally regulated silencing of the inactive X chromosome, as they are transiently enriched on the inactive X chromosome when X chromosome silencing is initiated. Here we analyze the dynamic localization of Suz12 during cellular differentiation and X-inactivation. Though Suz12 is a requisite member of the Eed/Ezh2 complexes, we found that Suz12 exhibits a notable difference from Ezh2 and Eed: while Ezh2 and Eed levels decrease during stem cell differentiation, Suz12 levels remain constant. Despite the differential regulation in abundance of Suz12 and Eed/Ezh2, Suz12 is also transiently enriched on the Xi during early stages of X-inactivation, and this accumulation is Xist RNA dependent. These results suggest that Suz12 may have a function that is not mediated by its association with Eed and Ezh2, and that this additional function is not involved in the regulation of X-inactivation.
染色质修饰是发育过程中基因重编程所必需的表观遗传改变之一。多梳蛋白家族(PcG)基因介导染色质修饰,促进发育调控的转录沉默。由Eed、Ezh2和Suz12组成的PcG蛋白复合物介导的组蛋白H3赖氨酸27三甲基化在分化、干细胞自我更新和肿瘤发生中不可或缺。Eed和Ezh2也与失活X染色体的发育调控沉默有关,因为在X染色体沉默开始时,它们会在失活X染色体上短暂富集。在这里,我们分析了Suz12在细胞分化和X染色体失活过程中的动态定位。虽然Suz12是Eed/Ezh2复合物的必要成员,但我们发现Suz12与Ezh2和Eed存在显著差异:在干细胞分化过程中,Ezh2和Eed水平下降,而Suz12水平保持不变。尽管Suz12和Eed/Ezh2在丰度上存在差异调节,但在X染色体失活早期,Suz12也会在Xi上短暂富集,且这种积累依赖于Xist RNA。这些结果表明,Suz12可能具有一种不通过与Eed和Ezh2结合介导的功能,并且这种额外功能不参与X染色体失活的调控。