The role of intergenic transcripts in the epigenetic control of rRNA gene transcription

核糖体基因存在于两种不同类型的染色质中，一种是允许转录的“开放”染色质，另一种是“封闭的”转录折射的染色质。维持活跃和沉默rDNA重复比率的机制尚不清楚，但沉默是影响转录活性的因素之一。RDNA沉默的干扰与衰老和人类遗传性疾病有关。这个项目的目标是了解DNA甲基化、转录活性和介导rDNA基因座沉默的蛋白质之间的关系。我们的项目将集中在(I)介导依赖甲基化的rDNA沉默的分子机制(Ii)组蛋白修饰对rRNA合成的参与，以及(Iii)ATRX蛋白在核糖体基因转录的表观遗传调控中的作用。从长远来看，这些研究将有助于理解通过细胞分裂传播rRNA基因活跃和沉默状态的机制，并将揭示表观遗传缺陷如何导致人类疾病。

Ribosomal genes exist in two distinct types of chromatin, an "open" one that is permissive to transcription and a "closed" one that is transcriptionally refractive. The mechanisms that maintain the ratio of active vs. silent rDNA repeats are poorly understood, but silencing is one of the factors that influences transcriptional activity. Perturbation of rDNA silencing has been implicated in aging and human hereditary diseases. The goal of this project is to understand the relationship between DNA methylation, transcriptional activity and the proteins that mediate silencing of the rDNA locus. Our project will focus on (i) the molecular mechanisms that mediate methylation-dependent silencing of rDNA (ii) the involvement of histone modifications on rRNA synthetis, and (iii) the role of ATRX protein in epigenetic regulation of ribosomal gene transcription. In the long term, these studies will lead to an understanding of the mechanisms that propagate the active and silent state of rRNA genes through cell division and will reveal how epigenetic defects cause human diseases.