Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell Biol. 2011 Sep;31(17):3569-83. doi: 10.1128/MCB.05590-11. Epub 2011 Jun 27.
In Saccharomyces cerevisiae, the Nrd1-Nab3-Sen1 pathway mediates the termination of snoRNAs and cryptic unstable transcripts (CUTs). Both Nrd1 and the Set1 histone H3K4 methyltransferase complex interact with RNA polymerase II (Pol II) during early elongation, leading us to test whether these two processes are functionally linked. The deletion of SET1 exacerbates the growth rate and termination defects of nrd1 mutants. Set1 is important for the appropriate recruitment of Nrd1. Additionally, Set1 modulates histone acetylation levels in the promoter-proximal region via the Rpd3L deacetylase and NuA3 acetyltransferase complexes, both of which contain PHD finger proteins that bind methylated H3K4. Increased levels of histone acetylation reduce the efficiency of Nrd1-dependent termination. We speculate that Set1 promotes proper early termination by the Nrd1-Nab3-Sen1 complex by affecting the kinetics of Pol II transcription in early elongation.
在酿酒酵母中，Nrd1-Nab3-Sen1 途径介导 snoRNA 和隐不稳定转录本 (CUTs) 的终止。Nrd1 和组蛋白 H3K4 甲基转移酶复合物 Set1 在早期延伸过程中都与 RNA 聚合酶 II (Pol II) 相互作用，这促使我们测试这两个过程是否在功能上相关。SET1 的缺失会加剧 nrd1 突变体的生长速度和终止缺陷。Set1 对于 Nrd1 的适当招募很重要。此外，Set1 通过 Rpd3L 去乙酰化酶和 NuA3 乙酰转移酶复合物调节启动子近端区域的组蛋白乙酰化水平，这两个复合物都含有结合甲基化 H3K4 的 PHD 指蛋白。组蛋白乙酰化水平的增加降低了 Nrd1 依赖性终止的效率。我们推测，Set1 通过影响早期延伸中 Pol II 转录的动力学，促进 Nrd1-Nab3-Sen1 复合物的正确早期终止。
