title: Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters.
abstract: Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes to interrogate 108 samples representing diverse perturbations. We identify 216 transcribed regions that encode putative lncRNAs, many with RT-PCR-validated periodic expression during the cell cycle, show altered expression in human cancers and are regulated in expression by specific oncogenic stimuli, stem cell differentiation or DNA damage. DNA damage induces five lncRNAs from the CDKN1A promoter, and one such lncRNA, named PANDA, is induced in a p53-dependent manner. PANDA interacts with the transcription factor NF-YA to limit expression of pro-apoptotic genes; PANDA depletion markedly sensitized human fibroblasts to apoptosis by doxorubicin. These findings suggest potentially widespread roles for promoter lncRNAs in cell-growth control.
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hung
authors.forename: Yulei
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael F
authors.initials: MF
authors.lastname: Lin
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Koegel
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Kotake
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Grant
authors.forename: Hugo M
authors.initials: HM
authors.lastname: Horlings
authors.forename: Nilay
authors.initials: N
authors.lastname: Shah
authors.forename: Christopher
authors.initials: C
authors.lastname: Umbricht
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kong
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Seung K
authors.initials: SK
authors.lastname: Kim
authors.forename: Marc
authors.initials: M
authors.lastname: van de Vijver
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.forename: Michael L
authors.initials: ML
authors.lastname: Whitfield
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Yue
authors.initials: Y
authors.lastname: Xiong
authors.forename: David J
authors.initials: DJ
authors.lastname: Wong
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D020869:Gene Expression Profiling; D018816:Genes, cdc / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D022661:RNA, Untranslated