We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters.
- Authors
Hung, Tiffany; Yulei Wang; Lin, Michael F.; Koegel, Ashley K.; Kotake, Yojiro; Grant, Gavin D.; Horlings, Hugo M.; Shah, Nilay; Umbricht, Christopher; Pei Wang; Yu Wang; Kong, Benjamin; Langerød, Anita; Børresen-Dale, Anne-Lise; Kim, Seung K.; van de Vijver, Marc; Sukumar, Saraswati; Whitfield, Michael L.; Kellis, Manolis; Yue Xiong
- 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.
- Subjects
RNA; CELL cycle; GENES; STEM cells; FIBROBLASTS
- Publication
Nature Genetics, 2011, Vol 43, Issue 7, p621
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.848