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


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.

SEEK ID: https://seek.lisym.org/publications/134

DOI: 10.1038/s41467-018-06611-5

Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

Publication type: Not specified

Journal: Nat Commun

Citation: Nat Commun 9(1) : 416

Date Published: 1st Dec 2018

Registered Mode: Not specified

Authors: 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, Jochen Hampe

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Brosch, M., Kattler, K., Herrmann, A., von Schönfels, W., Nordström, K., Seehofer, D., Damm, G., Becker, T., Zeissig, S., Nehring, S., Reichel, F., Moser, V., Thangapandi, R. V., Stickel, F., Baretton, G., Röcken, C., Muders, M., Matz-Soja, M., Krawczak, M., … Hampe, J. (2018). Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control. In Nature Communications (Vol. 9, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41467-018-06611-5

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Created: 20th Dec 2018 at 12:30

Last updated: 8th Mar 2024 at 07:44

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