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 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.
Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
Holger
H
Bierhoff
Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
Marcel Andre
MA
Dammert
Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
David
D
Brocks
Adolf Butenandt Institute and Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
Silvia
S
Dambacher
Adolf Butenandt Institute and Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
Gunnar
G
Schotta
Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. Electronic address: i.grummt@dkfz.de.
Ingrid
I
Grummt
D000818:Animals; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D007426:Genes, Intracisternal A-Particle; D020459:Genes, rRNA; D056426:Genetic Loci; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D041681:NIH 3T3 Cells; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics
D002843:Chromatin; D006657:Histones; D062085:RNA, Long Noncoding; C570043:Suv4-20h protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine