Tiffany Hung 1 , 2 , Yulei Wang 3 , Michael F. Lin 4 , 5 , Ashley K. Koegel 1 , 2 , Yojiro Kotake 6 , 7 , 8 , Gavin D. Grant 9 , Hugo M. Horlings 10 , Nilay Shah 11 , Christopher Umbricht 12 , Pei Wang 13 , Yu Wang 3 , Benjamin Kong 3 , Anita Langerod 14 , Anne-Lise Børresen-Dale 14 , 15 , Seung K. Kim 2 , 13 , Marc van de Vijver 10 , Saraswati Sukumar 11 , Michael L. Whitfield 9 , Manolis Kellis 4 , 5 , Yue Xiong 6 , David J. Wong 1 , Howard Y. Chang 1 , 2
05 June 2011
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 ultra-high 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.