TY  - INPR
A1  - Cattaneo, Paola
A1  - Hayes, Michael G. B.
A1  - Baumgarten, Nina
A1  - Hecker, Dennis
A1  - Peruzzo, Sofia
A1  - Kunderfranco, Paolo
A1  - Larcher, Veronica
A1  - Zhang, Lunfeng
A1  - Contu, Riccardo
A1  - Fonseca, Gregory
A1  - Spinozzi, Simone
A1  - Chen, Ju
A1  - Condorelli, Gianluigi
A1  - Schulz, Marcel Holger
A1  - Heinz, Sven
A1  - Guimarães-Camboa, Nuno
A1  - Evans, Sylvia M.
T1  - The epigenetic modifier DOT1L regulates gene regulatory networks necessary for cardiac patterning and cardiomyocyte cell cycle withdrawal
T2  - bioRxiv
N2  - Mechanisms by which specific histone modifications regulate distinct gene regulatory networks remain little understood. We investigated how H3K79me2, a modification catalyzed by DOT1L and previously considered a general transcriptional activation mark, regulates gene expression in mammalian cardiogenesis. Early embryonic cardiomyocyte ablation of Dot1l revealed that H3K79me2 does not act as a general transcriptional activator, but rather regulates highly specific gene regulatory networks at two critical cardiogenic junctures: left ventricle patterning and postnatal cardiomyocyte cell cycle withdrawal. Mechanistic analyses revealed that H3K79me2 in two distinct domains, gene bodies and regulatory elements, synergized to promote expression of genes activated by DOT1L. Surprisingly, these analyses also revealed that H3K79me2 in specific regulatory elements contributed to silencing genes usually not expressed in cardiomyocytes. As DOT1L mutants had increased numbers of postnatal mononuclear cardiomyocytes and prolonged cardiomyocyte cell cycle activity, controlled inhibition of DOT1L might be a strategy to promote cardiac regeneration post-injury.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73106
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-731061
IS  - 2022.10.18.512679
ER  -