title: Noncoding transcripts in sense and antisense orientation regulate the epigenetic state of ribosomal RNA genes.
abstract: Alternative transcription of the same gene in sense and antisense orientation regulates expression of protein-coding genes. Here we show that noncoding RNA (ncRNA) in sense and antisense orientation also controls transcription of rRNA genes (rDNA). rDNA exists in two types of chromatin--a euchromatic conformation that is permissive to transcription and a heterochromatic conformation that is transcriptionally silent. Silencing of rDNA is mediated by NoRC, a chromatin-remodeling complex that triggers heterochromatin formation. NoRC function requires RNA that is complementary to the rDNA promoter (pRNA). pRNA forms a DNA:RNA triplex with a regulatory element in the rDNA promoter, and this triplex structure is recognized by DNMT3b. The results imply that triplex-mediated targeting of DNMT3b to specific sequences may be a common pathway in epigenetic regulation. We also show that rDNA is transcribed in antisense orientation. The level of antisense RNA (asRNA) is down-regulated in cancer cells and up-regulated in senescent cells. Ectopic asRNA triggers trimethylation of histone H4 at lysine 20 (H4K20me3), suggesting that antisense transcripts guide the histone methyltransferase Suv4-20 to rDNA. The results reveal that noncoding RNAs in sense and antisense orientation are important determinants of the epigenetic state of rDNA.
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, D-69120 Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bierhoff
authors.forename: K
authors.initials: K
authors.lastname: Schmitz
authors.forename: F
authors.initials: F
authors.lastname: Maass
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: I
authors.initials: I
authors.lastname: Grummt
mesh_terms: D000107:Acetylation; D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D021901:DNA, Intergenic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic; D020459:Genes, rRNA / Q000235:genetics*; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D020871:RNA Stability / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D021901:DNA, Intergenic; D046912:Multiprotein Complexes; D016372:RNA, Antisense; D012333:RNA, Messenger; D022661:RNA, Untranslated; C499051:Baz2a protein, mouse; D000092468:Bromodomain Containing Proteins