title: A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response.
abstract: Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. mhuarte@broadinstitute.org
authors.forename: Maite
authors.initials: M
authors.lastname: Huarte
authors.forename: Mitchell
authors.initials: M
authors.lastname: Guttman
authors.forename: David
authors.initials: D
authors.lastname: Feldser
authors.forename: Manuel
authors.initials: M
authors.lastname: Garber
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Koziol
authors.forename: Daniela
authors.initials: D
authors.lastname: Kenzelmann-Broz
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Khalil
authors.forename: Or
authors.initials: O
authors.lastname: Zuk
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.forename: Michal
authors.initials: M
authors.lastname: Rabani
authors.forename: Laura D
authors.initials: LD
authors.lastname: Attardi
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
mesh_terms: D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D022661:RNA, Untranslated / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D022661:RNA, Untranslated; D016159:Tumor Suppressor Protein p53