Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma

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Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma. / Kreher, Stephan; Bouhlel, M Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan.

In: National Academy of Sciences. Proceedings, Vol. 111, No. 42, 21.10.2014, p. E4513–E4522.

Research output: Contribution to journalArticle

Harvard

Kreher, S, Bouhlel, MA, Cauchy, P, Lamprecht, B, Li, S, Grau, M, Hummel, F, Köchert, K, Anagnostopoulos, I, Jöhrens, K, Hummel, M, Hiscott, J, Wenzel, S-S, Lenz, P, Schneider, M, Küppers, R, Scheidereit, C, Giefing, M, Siebert, R, Rajewsky, K, Lenz, G, Cockerill, PN, Janz, M, Dörken, B, Bonifer, C & Mathas, S 2014, 'Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma', National Academy of Sciences. Proceedings, vol. 111, no. 42, pp. E4513–E4522. https://doi.org/10.1073/pnas.1406985111

APA

Kreher, S., Bouhlel, M. A., Cauchy, P., Lamprecht, B., Li, S., Grau, M., Hummel, F., Köchert, K., Anagnostopoulos, I., Jöhrens, K., Hummel, M., Hiscott, J., Wenzel, S-S., Lenz, P., Schneider, M., Küppers, R., Scheidereit, C., Giefing, M., Siebert, R., ... Mathas, S. (2014). Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma. National Academy of Sciences. Proceedings, 111(42), E4513–E4522. https://doi.org/10.1073/pnas.1406985111

Vancouver

Author

Kreher, Stephan ; Bouhlel, M Amine ; Cauchy, Pierre ; Lamprecht, Björn ; Li, Shuang ; Grau, Michael ; Hummel, Franziska ; Köchert, Karl ; Anagnostopoulos, Ioannis ; Jöhrens, Korinna ; Hummel, Michael ; Hiscott, John ; Wenzel, Sören-Sebastian ; Lenz, Peter ; Schneider, Markus ; Küppers, Ralf ; Scheidereit, Claus ; Giefing, Maciej ; Siebert, Reiner ; Rajewsky, Klaus ; Lenz, Georg ; Cockerill, Peter N ; Janz, Martin ; Dörken, Bernd ; Bonifer, Constanze ; Mathas, Stephan. / Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma. In: National Academy of Sciences. Proceedings. 2014 ; Vol. 111, No. 42. pp. E4513–E4522.

Bibtex

@article{b36c89f560ae4526a1d4935dfdd13b3a,
title = "Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma",
abstract = "Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.",
author = "Stephan Kreher and Bouhlel, {M Amine} and Pierre Cauchy and Bj{\"o}rn Lamprecht and Shuang Li and Michael Grau and Franziska Hummel and Karl K{\"o}chert and Ioannis Anagnostopoulos and Korinna J{\"o}hrens and Michael Hummel and John Hiscott and S{\"o}ren-Sebastian Wenzel and Peter Lenz and Markus Schneider and Ralf K{\"u}ppers and Claus Scheidereit and Maciej Giefing and Reiner Siebert and Klaus Rajewsky and Georg Lenz and Cockerill, {Peter N} and Martin Janz and Bernd D{\"o}rken and Constanze Bonifer and Stephan Mathas",
year = "2014",
month = oct
day = "21",
doi = "10.1073/pnas.1406985111",
language = "English",
volume = "111",
pages = "E4513–E4522",
journal = "National Academy of Sciences. Proceedings",
issn = "1091-6490",
publisher = "National Academy of Sciences",
number = "42",

}

RIS

TY - JOUR

T1 - Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma

AU - Kreher, Stephan

AU - Bouhlel, M Amine

AU - Cauchy, Pierre

AU - Lamprecht, Björn

AU - Li, Shuang

AU - Grau, Michael

AU - Hummel, Franziska

AU - Köchert, Karl

AU - Anagnostopoulos, Ioannis

AU - Jöhrens, Korinna

AU - Hummel, Michael

AU - Hiscott, John

AU - Wenzel, Sören-Sebastian

AU - Lenz, Peter

AU - Schneider, Markus

AU - Küppers, Ralf

AU - Scheidereit, Claus

AU - Giefing, Maciej

AU - Siebert, Reiner

AU - Rajewsky, Klaus

AU - Lenz, Georg

AU - Cockerill, Peter N

AU - Janz, Martin

AU - Dörken, Bernd

AU - Bonifer, Constanze

AU - Mathas, Stephan

PY - 2014/10/21

Y1 - 2014/10/21

N2 - Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.

AB - Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.

UR - http://www.pnas.org/content/111/42/E4513.long

U2 - 10.1073/pnas.1406985111

DO - 10.1073/pnas.1406985111

M3 - Article

C2 - 25288773

VL - 111

SP - E4513–E4522

JO - National Academy of Sciences. Proceedings

JF - National Academy of Sciences. Proceedings

SN - 1091-6490

IS - 42

ER -