Research output per year
Research output per year
Stephan Kreher, M Amine Bouhlel, Pierre Cauchy, Björn Lamprecht, Shuang Li, Michael Grau, Franziska Hummel, Karl Köchert, Ioannis Anagnostopoulos, Korinna Jöhrens, Michael Hummel, John Hiscott, Sören-Sebastian Wenzel, Peter Lenz, Markus Schneider, Ralf Küppers, Claus Scheidereit, Maciej Giefing, Reiner Siebert, Klaus Rajewsky
Research output: Contribution to journal › Article › peer-review
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.
Original language | English |
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Pages (from-to) | E4513–E4522 |
Journal | National Academy of Sciences. Proceedings |
Volume | 111 |
Issue number | 42 |
Early online date | 6 Oct 2014 |
DOIs | |
Publication status | Published - 21 Oct 2014 |
Research output: Contribution to journal › Article