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 Xiong; David J. Wong; Howard Y. Chang

doi:https://doi.org/10.1038/ng.848

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 journal › Article › Academic › peer-review

1008 Citations (Scopus)

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 language	English
Pages (from-to)	621-629
Journal	Nature Genetics
Volume	43
Issue number	7
DOIs	https://doi.org/10.1038/ng.848
Publication status	Published - 2011

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https://doi.org/10.1038/ng.848

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

@article{77c2a6b2ccc549b585ab62fb6ef50193,

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",

author = "Tiffany Hung and Yulei Wang and Lin, {Michael F.} and Koegel, {Ashley K.} and Yojiro Kotake and Grant, {Gavin D.} and Horlings, {Hugo M.} and Nilay Shah and Christopher Umbricht and Pei Wang and Yu Wang and Benjamin Kong and Anita Langer{\o}d and Anne-Lise B{\o}rresen-Dale and Kim, {Seung K.} and {van de Vijver}, Marc and Saraswati Sukumar and Whitfield, {Michael L.} and Manolis Kellis and Yue Xiong and Wong, {David J.} and Chang, {Howard Y.}",

year = "2011",

doi = "https://doi.org/10.1038/ng.848",

language = "English",

volume = "43",

pages = "621--629",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "7",

}

Hung, T, Wang, Y, Lin, MF, Koegel, AK, Kotake, Y, Grant, GD, Horlings, HM, Shah, N, Umbricht, C, Wang, P, Wang, Y, Kong, B, Langerød, A, Børresen-Dale, A-L, Kim, SK, van de Vijver, M, Sukumar, S, Whitfield, ML, Kellis, M, Xiong, Y, Wong, DJ & Chang, HY 2011, 'Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters', Nature Genetics, vol. 43, no. 7, pp. 621-629. https://doi.org/10.1038/ng.848

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T1 - Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters

AU - Hung, Tiffany

AU - Wang, Yulei

AU - Lin, Michael F.

AU - Koegel, Ashley K.

AU - Kotake, Yojiro

AU - Grant, Gavin D.

AU - Horlings, Hugo M.

AU - Shah, Nilay

AU - Umbricht, Christopher

AU - Wang, Pei

AU - Wang, Yu

AU - Kong, Benjamin

AU - Langerød, Anita

AU - Børresen-Dale, Anne-Lise

AU - Kim, Seung K.

AU - van de Vijver, Marc

AU - Sukumar, Saraswati

AU - Whitfield, Michael L.

AU - Kellis, Manolis

AU - Xiong, Yue

AU - Wong, David J.

AU - Chang, Howard Y.

PY - 2011

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N2 - 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

AB - 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

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DO - https://doi.org/10.1038/ng.848

M3 - Article

C2 - 21642992

SN - 1061-4036

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EP - 629

JO - Nature Genetics

JF - Nature Genetics

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ER -