Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control

Mario Brosch, Kathrin Kattler, Alexander Herrmann, Witigo von Schönfels, Karl Nordström, Daniel Seehofer, Georg Damm, Thomas Becker, Sebastian Zeissig, Sophie Nehring, Fabian Reichel, Vincent Moser, Raghavan Veera Thangapandi, Felix Stickel, Gustavo Baretton, Christoph Röcken, Michael Muders, Madlen Matz-Soja, Michael Krawczak, Gilles Gasparoni, Hella Hartmann, Andreas Dahl, Clemens Schafmayer, Jörn Walter and Jochen Hampe ()
Additional contact information
Mario Brosch: Technische Universität Dresden (TU Dresden)
Kathrin Kattler: Universität des Saarlandes
Alexander Herrmann: Technische Universität Dresden (TU Dresden)
Witigo von Schönfels: Christian-Albrechts-University Kiel
Karl Nordström: Universität des Saarlandes
Daniel Seehofer: University of Leipzig
Georg Damm: University of Leipzig
Thomas Becker: Christian-Albrechts-University Kiel
Sebastian Zeissig: Technische Universität Dresden (TU Dresden)
Sophie Nehring: Technische Universität Dresden (TU Dresden)
Fabian Reichel: Technische Universität Dresden (TU Dresden)
Vincent Moser: Technische Universität Dresden (TU Dresden)
Raghavan Veera Thangapandi: Technische Universität Dresden (TU Dresden)
Felix Stickel: University of Zürich
Gustavo Baretton: Technische Universität Dresden (TU Dresden)
Christoph Röcken: Christian-Albrechts-University Kiel
Michael Muders: Technische Universität Dresden (TU Dresden)
Madlen Matz-Soja: University of Leipzig
Michael Krawczak: Christian-Albrechts University
Gilles Gasparoni: Universität des Saarlandes
Hella Hartmann: Technische Universität Dresden (TU Dresden)
Andreas Dahl: Technische Universität Dresden (TU Dresden)
Clemens Schafmayer: Christian-Albrechts-University Kiel
Jörn Walter: Universität des Saarlandes
Jochen Hampe: Technische Universität Dresden (TU Dresden)

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.

Date: 2018
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DOI: 10.1038/s41467-018-06611-5

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