title: Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
abstract: Despite an abundance of studies on chromatin states and dynamics, there is an astonishing dearth of information on the expression of genes responsible for regulating histone and DNA modifications. We used here a set of 156 defined epigenetic modifier genes (EMG) and profiled their expression pattern in cells of different lineages. As reference value, expression data from human embryonic stem cells (hESC) were used. Hepatocyte-like cells were generated from hESC, and their EMG expression was compared to primary human liver cells. In parallel, we generated postmitotic human neurons (Lu d6), and compared their relative EMG expression to human cortex (Ctx). Clustering analysis of all cell types showed that neuronal lineage samples grouped together (94 similarly regulated EMG), as did liver cells (61 similarly-regulated), while the two lineages were clearly distinct. The general classification was followed by detailed comparison of the major EMG groups; genes that were higher expressed in differentiated cells than in hESC included the acetyltransferase KAT2B and the methyltransferase SETD7. Neuro-specific EMGs were the histone deacetylases HDAC5 and HDAC7, and the arginine-methyltransferase PRMT8. Comparison of young (Lu d6) and more aged (Ctx) neuronal samples suggested a maturation-dependent switch in the expression of functionally homologous proteins. For instance, the ratio of the histone H3 K27 methyltransfereases, EZH1 to EZH2, was high in Ctx and low in Lu d6. The same was observed for the polycomb repressive complex 1 (PRC1) subunits CBX7 and CBX8. A large proportion of EMGs in differentiated cells was very differently expressed than in hESC, and absolute levels were significantly higher in neuronal samples than in hepatic cells. Thus, there seem to be distinct qualitative and quantitative differences in EMG expression between cell lineages.
authors: Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany.
authors: Matthias K
authors: MK
authors: Weng
authors: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne (UKK), Cologne, Germany.
authors: Karthick
authors: K
authors: Natarajan
authors: Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany.
authors: Diana
authors: D
authors: Scholz
authors: Nycomed-Chair for Bioinformatics and Information Mining, Dept. of Computer and Information Science, University of Konstanz, Konstanz, Germany.
authors: Violeta N
authors: VN
authors: Ivanova
authors: Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne (UKK), Cologne, Germany.
authors: Agapios
authors: A
authors: Sachinidis
authors: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Technical University of Dortmund, Dortmund, Germany.
authors: Jan G
authors: JG
authors: Hengstler
authors: Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany.
authors: Tanja
authors: T
authors: Waldmann
authors: Doerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Konstanz, Germany.
authors: Marcel
authors: M
authors: Leist
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism; D057890:Epigenomics; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*