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

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

Fingerprint

Long Noncoding RNA
Untranslated RNA
Cell Cycle
DNA Damage
cdc Genes
Regulator Genes
Doxorubicin
Genes
Cell Differentiation
Transcription Factors
Stem Cells
Fibroblasts
Apoptosis
Polymerase Chain Reaction
Growth
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Hung, T., Wang, Y., Lin, M. F., Koegel, A. K., Kotake, Y., Grant, G. D., ... 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

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.

In: Nature Genetics, Vol. 43, No. 7, 07.2011, p. 621-629.

Research output: Contribution to journalArticle

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, AL, 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
Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nature Genetics. 2011 Jul;43(7):621-629. https://doi.org/10.1038/ng.848
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. / Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. In: Nature Genetics. 2011 ; Vol. 43, No. 7. pp. 621-629.
@article{14bc7e02794e4c4d881e048d3ee1df13,
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 B{\o}rresen-Dale, {Anne Lise} 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",
month = "7",
doi = "10.1038/ng.848",
language = "English (US)",
volume = "43",
pages = "621--629",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

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 - 2011/7

Y1 - 2011/7

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.

UR - http://www.scopus.com/inward/record.url?scp=79959756263&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959756263&partnerID=8YFLogxK

U2 - 10.1038/ng.848

DO - 10.1038/ng.848

M3 - Article

C2 - 21642992

AN - SCOPUS:79959756263

VL - 43

SP - 621

EP - 629

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -