Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

Tiffany Hung, Yulei Wang, Michael F. Lin, Ashley K. Koegel, Yojiro Kotake, Gavin D. Grant, Hugo M. Horlings, Nilay Shah, Christopher Umbricht, Pei Wang, Yu Wang, Benjamin Kong, Anita Langerød, Anne Lise Børresen-Dale, Seung K. Kim, Marc Van De Vijver, Saraswati Sukumar, Michael L. Whitfield, Manolis Kellis, Yue XiongDavid J. Wong, Howard Y. Chang

Research output: Contribution to journalArticle

714 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)621-629
Number of pages9
JournalNature Genetics
Volume43
Issue number7
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Hung, T., Wang, Y., Lin, M. F., Koegel, A. K., Kotake, Y., Grant, G. D., Horlings, H. M., Shah, N., Umbricht, C., Wang, P., Wang, Y., Kong, B., Langerød, A., Børresen-Dale, A. L., Kim, S. K., Van De Vijver, M., Sukumar, S., Whitfield, M. L., Kellis, M., ... Chang, H. Y. (2011). Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nature Genetics, 43(7), 621-629. https://doi.org/10.1038/ng.848