Quiescence-Induced LncRNAs Trigger H4K20 Trimethylation and Transcriptional Silencing

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...

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Bibliographic Details
Published in:Molecular cell 2014-05, Vol.54 (4), p.675-682
Main Authors: Bierhoff, Holger, Dammert, Marcel Andre, Brocks, David, Dambacher, Silvia, Schotta, Gunnar, Grummt, Ingrid
Format: Article
Language:English
Subjects:
Animals
Cell Proliferation
Chromatin - genetics
Chromatin - metabolism
Gene Expression Regulation
Gene Silencing
Genes, Intracisternal A-Particle
Genes, rRNA
Genetic Loci
Histone-Lysine N-Methyltransferase - genetics
Histone-Lysine N-Methyltransferase - metabolism
Histones - chemistry
Histones - genetics
Histones - metabolism
Lysine - metabolism
Methylation
Mice
NIH 3T3 Cells
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
Telomere - genetics
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Summary: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. [Display omitted] •PAPAS, a lncRNA in antisense orientation to rDNA, is upregulated in quiescent cells•PAPAS interacts with Suv4-20h2 and mediates H4K20me3 at rDNA•H4K20me3 induces global chromatin compaction upon quiescence•LncRNAs mediate H4K20me3 and chromatin compaction at IAP retrotransposons The switch from cellular proliferation to quiescence is linked to transcriptional downregulation. Bierhoff et al. show that upon growth arrest rRNA genes and IAP retroelements are epigentically silenced by long noncoding RNAs (lncRNAs), which mediate histone H4 lysine 20 trimethylation (H4K20me3) by recruiting the methyltransferase Suv4-20h2.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2014.03.032