Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genetics. 2012 Aug;191(4):1119-28. doi: 10.1534/genetics.112.141242. Epub 2012 May 29.
The rDNA genes are transcribed by RNA polymerase I to make structural RNAs for ribosomes. Hundreds of rDNA genes are typically arranged in an array that spans megabase pairs of DNA. These arrays are the major sites of transcription in growing cells, accounting for as much as 50% of RNA synthesis. The repetitive rDNA arrays are thought to use heterochromatic gene silencing as a mechanism for metabolic regulation, since repeated sequences nucleate heterochromatin formation in eukaryotes. Drosophila melanogaster carries an rDNA array on the X chromosome and on the Y chromosome, and genetic analysis has suggested that both are transcribed. However, using a chromatin-marking assay, we find that the entire X chromosome rDNA array is normally silenced in D. melanogaster males, while the Y chromosome rDNA array is dominant and expressed. This resembles "nucleolar dominance," a phenomenon that occurs in interspecific hybrids where an rDNA array from one parental species is silenced, and that from the other parent is preferentially transcribed. Interspecies nucleolar dominance is thought to result from incompatibilities between species-specific transcription factors and the rDNA promoters in the hybrid, but our results show that nucleolar dominance is a normal feature of rDNA regulation. Nucleolar dominance within D. melanogaster is only partially dependent on known components of heterochromatic gene silencing, implying that a distinctive chromatin regulatory system may act at rDNA genes. Finally, we isolate variant Y chromosomes that allow X chromosome array expression and suggest that the large-scale organization of rDNA arrays contribute to nucleolar dominance. This is the first example of allelic inactivation in D. melanogaster.
rDNA 基因由 RNA 聚合酶 I 转录,为核糖体生成结构 RNA。数百个 rDNA 基因通常排列在一个跨越兆碱基对 DNA 的序列中。这些序列是生长细胞中主要的转录位点,占 RNA 合成的 50%之多。重复的 rDNA 序列被认为利用异染色质基因沉默作为代谢调节的一种机制,因为在真核生物中,重复序列引发异染色质形成。果蝇携带 X 染色体和 Y 染色体上的 rDNA 序列,遗传分析表明这两个染色体上的 rDNA 序列都能转录。然而,我们通过染色质标记检测发现,在雄性果蝇中,整个 X 染色体 rDNA 序列通常处于沉默状态,而 Y 染色体 rDNA 序列则是显性的并表达。这类似于“核仁优势”,这是一种发生在种间杂种中的现象,其中一个亲本物种的 rDNA 序列被沉默,而另一个亲本物种的 rDNA 序列则被优先转录。种间核仁优势被认为是由于杂种中物种特异性转录因子与 rDNA 启动子之间的不兼容性造成的,但我们的结果表明,核仁优势是 rDNA 调控的一个正常特征。果蝇中的核仁优势仅部分依赖于已知的异染色质基因沉默成分,这表明可能有一种独特的染色质调控系统作用于 rDNA 基因。最后,我们分离出允许 X 染色体序列表达的变体 Y 染色体,并提出 rDNA 序列的大规模组织有助于核仁优势。这是果蝇中首次发现等位基因失活的现象。