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Paper of the Month

March 2020


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The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition. PNAS (2020), DZHK authors: Simone F. Glaser, Andreas W. Heumüller, Lukas Tombor, Patrick Hofmann, Stefan Günther, David Hassel, Reinier A. Boon, Wesley Abplanalp, David John, Stefanie Dimmeler

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Endothelial cells play an important role in maintenance of the vascular system and the repair after injury. Under pro-inflammatory conditions, endothelial cells can acquire a mesenchymal phenotype by a process named endothelial-to-mesenchymal transition (EndMT). EndMT occurs e.g. during the development of the cardiac valves or in adult during pathological conditions such as organ fibrosis or atherosclerosis. Various cytokines and stimuli have been shown to be involved in the induction or inhibition of EndMT, such as TGF-β family or different flow conditions.

Hallmarks of EndMT are changes in gene expression, endothelial marker are down-regulated whereas mesenchymal markers were up-regulated. Gene expression can be regulated by epigenetic mechanisms, such as the methylation of DNA or acetylation and methylation of histones, which regulate the accessibility of the chromatin for transcriptional machinery.

One well known class of proteins which change the epigenetic modification on histones are the demethylases JmjC domain containing proteins with their family member JMJD2B.Since a regulation of EndMT by histone-demethylases is still unclear, researchers of the German Centre for Cardiovascular Research (DZHK), led by Professor Stefanie Dimmeler, Institute for cardiovascular Regeneration Goethe University Frankfurt am Main, investigated the epigenetic control of EndMT by the histone demethylase JMJD2B.

The results of their studies are published in the renowned journal “Proceedings of the National Academy of Sciences of the United States of Amerika (PNAS)” February 25, 2020. The study reveals that endothelial identity and function is epigenetically controlled by the histone demethylase JMJD2B, which is induced by EndMT-promoting pro-inflammatory, disturbed flow and hypoxic conditions and support the acquirement of a mesenchymal phenotype.

In vitro and in vivo findings showed reduced levels of EndMT induction after silencing of Jmj2b in endothelial cells and in the heart after acute myocardial infarct. Thereby, JMJD2B regulates the methylation states of the histone H3K9 in the promoter region of target genes such as the mesenchymal marker Calponin and genes involved in TGF-β signaling, such as AKT Serine/Threonine Kinase 3 (AKT3) and sulfatase 1 (SULF1).

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