Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control
Year: 2018
Type: article
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.
Source: Nature Communications
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
Institutions: Center for Regenerative Therapies Dresden, Technische Universität Dresden, Saarland University, Christian-Albrechts-Universität zu Kiel, University Hospital Schleswig-Holstein, University Hospital Leipzig, Leipzig University, University of Zurich, Center for Molecular and Cellular Bioengineering
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: LiSyM - Verbundprojekt: Pillar I - Metabolischer Frühschaden (EMI), TP6, de.NBI - Partner - de.NBI-epi, Dynamic bile flow modelling and cellular sensing in primary sclerosing cholangitis, Verbundvorhaben: EpiTrio 'Integrative Epigenomic der Fettleibigkeit und ihrer metabolischen Komplikationen', TU Dresden, G7730578286, LiSyM - Verbundprojekt: Pillar I - Metabolischer Frühschaden (EMI), TP8, Verbundprojekt: Deutsches Epigenom Programm (DEEP) TP 3-1 'Wissenschaftliche Verbundkoordination', TP 3-2 'Organisatorische Verbundkoordination', TP 3-3 'IHEC bezogene Kommunikationsplattform', TP 2-1 'DANN Methylierungs- und Dnase I-Kartierung', TP 4-2 'Epigenetik und Steatose und Steatohepatitis'.
OpenAlex ID: W2895048801