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Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping

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Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping. / Schörg, Alexandra; Santambrogio, Sara; Platt, James L; Schödel, Johannes; Lindenmeyer, Maja T; Cohen, Clemens D; Schrödter, Katrin; Mole, David R; Wenger, Roland H; Hoogewijs, David.

In: NUCLEIC ACIDS RES, Vol. 43, No. 12, 13.07.2015, p. 5810-23.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schörg, A, Santambrogio, S, Platt, JL, Schödel, J, Lindenmeyer, MT, Cohen, CD, Schrödter, K, Mole, DR, Wenger, RH & Hoogewijs, D 2015, 'Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping', NUCLEIC ACIDS RES, vol. 43, no. 12, pp. 5810-23. https://doi.org/10.1093/nar/gkv506

APA

Schörg, A., Santambrogio, S., Platt, J. L., Schödel, J., Lindenmeyer, M. T., Cohen, C. D., Schrödter, K., Mole, D. R., Wenger, R. H., & Hoogewijs, D. (2015). Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping. NUCLEIC ACIDS RES, 43(12), 5810-23. https://doi.org/10.1093/nar/gkv506

Vancouver

Schörg A, Santambrogio S, Platt JL, Schödel J, Lindenmeyer MT, Cohen CD et al. Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping. NUCLEIC ACIDS RES. 2015 Jul 13;43(12):5810-23. https://doi.org/10.1093/nar/gkv506

Bibtex

@article{1a92ec14074c4153858595cf83a82c33,
title = "Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping",
abstract = "A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the -82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the -82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the -82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia. ",
keywords = "Adaptor Proteins, Signal Transducing, Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Hypoxia, Cell Line, Chromatin, HeLa Cells, Humans, Hypoxia-Inducible Factor 1, Membrane Proteins, Mice, Mice, Inbred C57BL, Phosphoproteins, Promoter Regions, Genetic, Response Elements, Signal Transduction, Transcriptional Activation, src-Family Kinases, Journal Article, Research Support, Non-U.S. Gov't",
author = "Alexandra Sch{\"o}rg and Sara Santambrogio and Platt, {James L} and Johannes Sch{\"o}del and Lindenmeyer, {Maja T} and Cohen, {Clemens D} and Katrin Schr{\"o}dter and Mole, {David R} and Wenger, {Roland H} and David Hoogewijs",
note = "{\textcopyright} The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2015",
month = jul,
day = "13",
doi = "10.1093/nar/gkv506",
language = "English",
volume = "43",
pages = "5810--23",
journal = "NUCLEIC ACIDS RES",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping

AU - Schörg, Alexandra

AU - Santambrogio, Sara

AU - Platt, James L

AU - Schödel, Johannes

AU - Lindenmeyer, Maja T

AU - Cohen, Clemens D

AU - Schrödter, Katrin

AU - Mole, David R

AU - Wenger, Roland H

AU - Hoogewijs, David

N1 - © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2015/7/13

Y1 - 2015/7/13

N2 - A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the -82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the -82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the -82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia.

AB - A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the -82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the -82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the -82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia.

KW - Adaptor Proteins, Signal Transducing

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Cell Hypoxia

KW - Cell Line

KW - Chromatin

KW - HeLa Cells

KW - Humans

KW - Hypoxia-Inducible Factor 1

KW - Membrane Proteins

KW - Mice

KW - Mice, Inbred C57BL

KW - Phosphoproteins

KW - Promoter Regions, Genetic

KW - Response Elements

KW - Signal Transduction

KW - Transcriptional Activation

KW - src-Family Kinases

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/nar/gkv506

DO - 10.1093/nar/gkv506

M3 - SCORING: Journal article

C2 - 26007655

VL - 43

SP - 5810

EP - 5823

JO - NUCLEIC ACIDS RES

JF - NUCLEIC ACIDS RES

SN - 0305-1048

IS - 12

ER -