Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/87031 |
| _version_ | 1826217436844654592 |
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| author | Hung, Tiffany Wang, Yulei Lin, Michael F. Koegel, Ashley K. Kotake, Yojiro Grant, Gavin D. Horlings, Hugo M. Shah, Nilay Umbricht, Christopher Wang, Pei Wang, Yu Kong, Benjamin Langerød, Anita Børresen-Dale, Anne-Lise Kim, Seung K. van de Vijver, Marc Sukumar, Saraswati Whitfield, Michael L. Kellis, Manolis Xiong, Yue Wong, David J. Chang, Howard Y. Lin, Michael F. |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Hung, Tiffany Wang, Yulei Lin, Michael F. Koegel, Ashley K. Kotake, Yojiro Grant, Gavin D. Horlings, Hugo M. Shah, Nilay Umbricht, Christopher Wang, Pei Wang, Yu Kong, Benjamin Langerød, Anita Børresen-Dale, Anne-Lise Kim, Seung K. van de Vijver, Marc Sukumar, Saraswati Whitfield, Michael L. Kellis, Manolis Xiong, Yue Wong, David J. Chang, Howard Y. Lin, Michael F. |
| author_sort | Hung, Tiffany |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T17:03:38Z |
| format | Article |
| id | mit-1721.1/87031 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:03:38Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/870312022-09-29T23:24:16Z Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters Hung, Tiffany Wang, Yulei Lin, Michael F. Koegel, Ashley K. Kotake, Yojiro Grant, Gavin D. Horlings, Hugo M. Shah, Nilay Umbricht, Christopher Wang, Pei Wang, Yu Kong, Benjamin Langerød, Anita Børresen-Dale, Anne-Lise Kim, Seung K. van de Vijver, Marc Sukumar, Saraswati Whitfield, Michael L. Kellis, Manolis Xiong, Yue Wong, David J. Chang, Howard Y. Lin, Michael F. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Lin, Michael F. Kellis, Manolis 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. National Institutes of Health (U.S.) National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (NIAMS) (K08-AR054615)) National Cancer Institute (U.S.) (NIH/(NCI) (R01-CA118750)) National Cancer Institute (U.S.) (NIH/(NCI) R01-CA130795)) Juvenile Diabetes Research Foundation International American Cancer Society Howard Hughes Medical Institute (Early career scientist) Stanford University (Graduate Fellowship) National Science Foundation (U.S.) (Graduate Research Fellowship) United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship) 2014-05-16T16:50:27Z 2014-05-16T16:50:27Z 2011-06 2010-08 Article http://purl.org/eprint/type/JournalArticle 1061-4036 1546-1718 http://hdl.handle.net/1721.1/87031 Hung, Tiffany, Yulei Wang, Michael F Lin, Ashley K Koegel, Yojiro Kotake, Gavin D Grant, Hugo M Horlings, et al. “Extensive and Coordinated Transcription of Noncoding RNAs Within Cell-Cycle Promoters.” Nature Genetics 43, no. 7 (June 5, 2011): 621–629. en_US http://dx.doi.org/10.1038/ng.848 Nature Genetics Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Hung, Tiffany Wang, Yulei Lin, Michael F. Koegel, Ashley K. Kotake, Yojiro Grant, Gavin D. Horlings, Hugo M. Shah, Nilay Umbricht, Christopher Wang, Pei Wang, Yu Kong, Benjamin Langerød, Anita Børresen-Dale, Anne-Lise Kim, Seung K. van de Vijver, Marc Sukumar, Saraswati Whitfield, Michael L. Kellis, Manolis Xiong, Yue Wong, David J. Chang, Howard Y. Lin, Michael F. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters |
| title | Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters |
| title_full | Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters |
| title_fullStr | Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters |
| title_full_unstemmed | Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters |
| title_short | Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters |
| title_sort | extensive and coordinated transcription of noncoding rnas within cell cycle promoters |
| url | http://hdl.handle.net/1721.1/87031 |
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