Negative epigenetic regulation of rRNA expression

Transcription of rRNA genes is controlled by epigenetic activation and repression (reviewed in McStay and Grummt 2008, Goodfellow and Zomerdijk 2012, Grummt and Langst 2013). About half of the roughly 400 rRNA genes are expressed and these have the modifications of active chromatin: unmethylated DNA and acetylated histones. Repressed genes generally have methylated DNA and histone H3 methylated at lysine-9. Regulators of repression include the eNoSC complex, SIRT1, and the NoRC complex.<br> SIRT1 negatively regulates rRNA expression as a subunit of the eNoSC complex, which deacetylates histone H3 and dimethylates lysine-9 of histone H3 (H3K9me2).<br>NoRC negatively regulates rRNA expression by shifting a nucleosome near the start of rRNA transcription into a more repressive location and recruiting Histone Deacetylase 1 and 2 (HDAC1, HDAC2) and DNA Methyltransferase 1 and 3b (DNMT1, DNMT3b).

rRNA基因的转录受表观遗传激活与抑制的调控（详见McStay与Grummt于2008年、Goodfellow与Zomerdijk于2012年、Grummt与Langst于2013年的综述）。在约400个rRNA基因中，大约一半得到表达，并具有活性染色质的特征：未甲基化的DNA和乙酰化的组蛋白。受抑制的基因通常具有甲基化的DNA和组蛋白H3在赖氨酸-9位点的甲基化。抑制剂的调控机制包括eNoSC复合物、SIRT1和NoRC复合物。
SIRT1作为eNoSC复合物的一个亚基，负向调控rRNA的表达，其通过去乙酰化组蛋白H3和甲基化组蛋白H3的赖氨酸-9（H3K9me2）来实现。
NoRC通过将接近rRNA转录起始点的核小体转移到更加抑制的位置，并募集组蛋白脱乙酰化酶1和2（HDAC1，HDAC2）以及DNA甲基转移酶1和3b（DNMT1，DNMT3b）来负向调控rRNA的表达。