核糖体DNA基因座的等位基因失活
Allelic inactivation of rDNA loci.
作者信息
Schlesinger Sharon, Selig Sara, Bergman Yehudit, Cedar Howard
机构信息
Department of Cellular Biochemistry and Experimental Medicine, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel.
出版信息
Genes Dev. 2009 Oct 15;23(20):2437-47. doi: 10.1101/gad.544509.
Abstract
Human cells contain several hundred ribosomal genes (rDNA) that are clustered into nucleolar organizer regions (NORs) on the short arms of five different acrocentric chromosomes. Only approximately 50% of the gene copies are actually expressed in somatic cells. Here, we used a new cytological technique to demonstrate that rDNA is regulated allelically in a regional manner, with one parental copy of each NOR being repressed in any individual cell. This process is similar to that of X-chromosome inactivation in females. Early in development, one copy of each NOR becomes late-replicating, thus probably marking it for inactivation and subsequent targeted de novo methylation at rDNA promoter regions. Once established, this multichromosomal allelic pattern is then maintained clonally in somatic cells. This pathway may serve as an epigenetic mechanism for controlling the number of available rDNA copies during development.
摘要
人类细胞含有数百个核糖体基因（rDNA），这些基因聚集在五条不同近端着丝粒染色体短臂上的核仁组织区（NORs）。实际上，只有约50%的基因拷贝在体细胞中表达。在这里，我们使用一种新的细胞学技术来证明rDNA以区域方式进行等位基因调控，每个NOR的一个亲本拷贝在任何单个细胞中被抑制。这个过程类似于雌性中X染色体失活的过程。在发育早期，每个NOR的一个拷贝变得复制延迟，因此可能标志着它将被失活，并随后在rDNA启动子区域进行靶向从头甲基化。一旦确立，这种多染色体等位基因模式随后在体细胞中克隆性维持。这条途径可能作为一种表观遗传机制，在发育过程中控制可用rDNA拷贝的数量。
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