Extensive regulation of the non-coding transcriptome by hypoxia: role of HIF in releasing paused RNApol2

被引：135

作者：

Choudhry, Hani ^{[1
,2
]}

Schoedel, Johannes ^{[3
,4
]}

Oikonomopoulos, Spyros ^{[1
]}

Camps, Carme ^{[1
]}

Grampp, Steffen ^{[4
]}

Harris, Adrian L. ^{[5
]}

Ratcliffe, Peter J. ^{[3
]}

Ragoussis, Jiannis ^{[1
,6
,7
,8
]}

Mole, David R. ^{[3
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[2] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah, Saudi Arabia

[3] Univ Oxford, Oxford, England

[4] Univ Erlangen Nurnberg, Dept Hypertens & Nephrol, D-91054 Erlangen, Germany

[5] Univ Oxford, Weatherall Inst Mol Med, Oxford, England

[6] McGill Univ, Montreal, PQ, Canada

[7] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[8] BSRC Alexander Fleming, Athens, Greece

来源：

EMBO REPORTS | 2014年 / 15卷 / 01期

基金：

英国惠康基金;

关键词：

HIF; hypoxia; non-coding; RNApol2; transcription; BINDING SITES; HUMAN GENOME; CANCER; RNAS; EXPRESSION; METAZOANS; SET1; P53;

D O I：

10.1002/embr.201337642

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hypoxia is central to both ischaemic and neoplastic diseases. However, the non-coding transcriptional response to hypoxia is largely uncharacterized. We undertook integrated genomic analyses of both non-coding and coding transcripts using massively parallel sequencing and interfaced this data with pan-genomic analyses of hypoxia-inducible factor (HIF) and RNApol2 binding in hypoxic cells. These analyses revealed that all classes of RNA are profoundly regulated by hypoxia and implicated HIF as a major direct regulator of both the non-coding and coding transcriptome, acting predominantly through release of pre-bound promoter-paused RNApol2. These findings indicate that the transcriptional response to hypoxia is substantially more extensive than previously considered.

引用

页码：70 / 76

页数：7

共 22 条

[1] Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans [J].

Adelman, Karen ;

Lis, John T. .

NATURE REVIEWS GENETICS, 2012, 13 (10) :720-731

[2] High-resolution profiling of histone methylations in the human genome [J].

Barski, Artern ;

Cuddapah, Suresh ;

Cui, Kairong ;

Roh, Tae-Young ;

Schones, Dustin E. ;

Wang, Zhibin ;

Wei, Gang ;

Chepelev, Iouri ;

Zhao, Keji .

CELL, 2007, 129 (04) :823-837

[3] An Architectural Role for a Nuclear Noncoding RNA: NEAT1 RNA Is Essential for the Structure of Paraspeckles [J].

Clemson, Christine M. ;

Hutchinson, John N. ;

Sara, Sergio A. ;

Ensminger, Alexander W. ;

Fox, Archa H. ;

Chess, Andrew ;

Lawrence, Jeanne B. .

MOLECULAR CELL, 2009, 33 (06) :717-726

[4] An integrated encyclopedia of DNA elements in the human genome [J].

Dunham, Ian ;

Kundaje, Anshul ;

Aldred, Shelley F. ;

Collins, Patrick J. ;

Davis, CarrieA. ;

Doyle, Francis ;

Epstein, Charles B. ;

Frietze, Seth ;

Harrow, Jennifer ;

Kaul, Rajinder ;

Khatun, Jainab ;

Lajoie, Bryan R. ;

Landt, Stephen G. ;

Lee, Bum-Kyu ;

Pauli, Florencia ;

Rosenbloom, Kate R. ;

Sabo, Peter ;

Safi, Alexias ;

Sanyal, Amartya ;

Shoresh, Noam ;

Simon, Jeremy M. ;

Song, Lingyun ;

Trinklein, Nathan D. ;

Altshuler, Robert C. ;

Birney, Ewan ;

Brown, James B. ;

Cheng, Chao ;

Djebali, Sarah ;

Dong, Xianjun ;

Dunham, Ian ;

Ernst, Jason ;

Furey, Terrence S. ;

Gerstein, Mark ;

Giardine, Belinda ;

Greven, Melissa ;

Hardison, Ross C. ;

Harris, Robert S. ;

Herrero, Javier ;

Hoffman, Michael M. ;

Iyer, Sowmya ;

Kellis, Manolis ;

Khatun, Jainab ;

Kheradpour, Pouya ;

Kundaje, Anshul ;

Lassmann, Timo ;

Li, Qunhua ;

Lin, Xinying ;

Marinov, Georgi K. ;

Merkel, Angelika ;

Mortazavi, Ali .

NATURE, 2012, 489 (7414) :57-74

[5] Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition -: The role of HIF-1α, HIF-2α, and other pathways [J].

Elvidge, Gareth P. ;

Glenny, Louisa ;

Appelhoff, Rebecca J. ;

Ratcliffe, Peter J. ;

Ragoussis, Jiannis ;

Gleadle, Jonathan M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (22) :15215-15226

[6] Non-coding RNAs in human disease [J].

Esteller, Manel .

NATURE REVIEWS GENETICS, 2011, 12 (12) :861-874

[7] Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway [J].

Kaelin, William G., Jr. ;

Ratcliffe, Peter J. .

MOLECULAR CELL, 2008, 30 (04) :393-402

[8] CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine [J].

Kong, Lei ;

Zhang, Yong ;

Ye, Zhi-Qiang ;

Liu, Xiao-Qiao ;

Zhao, Shu-Qi ;

Wei, Liping ;

Gao, Ge .

NUCLEIC ACIDS RESEARCH, 2007, 35 :W345-W349

[9] The oncofetal H19 RNA connection: Hypoxia, p53 and cancer [J].

Matouk, Imad J. ;

Mezan, Shaul ;

Mizrahi, Aya ;

Ohana, Patricia ;

Abu-lail, Rasha ;

Fellig, Yakov ;

deGroot, Nathan ;

Galun, Eithan ;

Hochberg, Abraham .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2010, 1803 (04) :443-451

[10] The Role of Hypoxia Regulated microRNAs in Cancer [J].

McCormick, Robert ;

Buffa, Francesca M. ;

Ragoussis, Jiannis ;

Harris, Adrian L. .

DIVERSE EFFECTS OF HYPOXIA ON TUMOR PROGRESSION, 2010, 345 :47-70

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