Quiescence-Induced LncRNAs Trigger H4K20 Trimethylation and Transcriptional Silencing

被引:152
作者
Bierhoff, Holger [1 ]
Dammert, Marcel Andre [1 ]
Brocks, David [1 ]
Dambacher, Silvia [2 ,3 ]
Schotta, Gunnar [2 ,3 ]
Grummt, Ingrid [1 ]
机构
[1] DKFZ ZMBH Alliance, Div Mol Biol Cell 2, German Canc Res Ctr, D-69120 Heidelberg, Germany
[2] Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany
[3] Univ Munich, Ctr Integrated Prot Sci Munich, D-80336 Munich, Germany
基金
欧洲研究理事会;
关键词
HETEROCHROMATIN FORMATION; RNA; LANDSCAPE; RETROTRANSPOSITION; DIFFERENTIATION; RECRUITMENT; NUCLEOSOME; ELEMENTS;
D O I
10.1016/j.molcel.2014.03.032
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
A complex network of regulatory pathways links transcription to cell growth and proliferation. Here we show that cellular quiescence alters chromatin structure by promoting trimethylation of histone H4 at lysine 20 (H4K20me3). In contrast to pericentric or telomeric regions, recruitment of the H4K20 methyltransferase Suv4-20h2 to rRNA genes and IAP elements requires neither trimethylation of H3K9 nor interaction with HP1 proteins but depends on long noncoding RNAs (lncRNAs) that interact with Suv4-20h2. Growth factor deprivation and terminal differentiation lead to upregulation of these lncRNAs, increase in H4K20me3, and chromatin compaction. The results uncover a lncRNA-mediated mechanism that guides Suv4-20h2 to specific genomic loci to establish a more compact chromatin structure in growth-arrested cells.
引用
收藏
页码:675 / 682
页数:8
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