Li Chonghua, Mueller John E, Elfline Megan, Bryk Mary
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
Mol Microbiol. 2008 Feb;67(4):906-19. doi: 10.1111/j.1365-2958.2007.06101.x. Epub 2008 Jan 7.
Several epigenetic phenomena occur at ribosomal DNA loci in eukaryotic cells, including the silencing of Pol I and Pol II transcribed genes, silencing of replication origins and repression of recombination. In Saccharomyces cerevisiae, studies focusing on the silencing of Pol II transcription and genetic recombination at the ribosomal DNA locus (rDNA) have provided insight into the mechanisms through which chromatin and chromatin-associated factors regulate gene expression and chromosome stability. The core histones, H2A, H2B, H3 and H4, the fundamental building blocks of chromatin, have been shown to regulate silent chromatin at the rDNA; however, the function of the linker histone H1 has not been well characterized. Here, we show that S. cerevisiae histone H1 represses recombination at the rDNA without affecting Pol II gene silencing. The most highly studied repressor of recombination at the rDNA is the Silent information regulator protein Sir2. We find that cells lacking histone H1 do not exhibit a premature-ageing phenotype nor do they accumulate the rDNA recombination intermediates and products that are found in cells lacking Sir2. These results suggest that histone H1 represses recombination at the rDNA by a mechanism that is independent of the recombination pathways regulated by Sir2.
几种表观遗传现象发生在真核细胞的核糖体DNA位点，包括RNA聚合酶I和RNA聚合酶II转录基因的沉默、复制起点的沉默以及重组的抑制。在酿酒酵母中，针对核糖体DNA位点（rDNA）处RNA聚合酶II转录的沉默和基因重组的研究，为染色质及染色质相关因子调控基因表达和染色体稳定性的机制提供了见解。核心组蛋白H2A、H2B、H3和H4作为染色质的基本组成部分，已被证明可调控rDNA处的沉默染色质；然而，连接组蛋白H1的功能尚未得到充分表征。在此，我们表明酿酒酵母组蛋白H1可抑制rDNA处的重组，而不影响RNA聚合酶II基因的沉默。rDNA处研究最多的重组抑制因子是沉默信息调节蛋白Sir2。我们发现，缺乏组蛋白H1的细胞既不表现出早衰表型，也不会积累在缺乏Sir2的细胞中发现的rDNA重组中间体和产物。这些结果表明，组蛋白H1通过一种独立于Sir2调控的重组途径的机制来抑制rDNA处的重组。
