Vol 9: Lineage-Specific Regulation of Epigenetic Modifier Genes in Human Liver and Brain.Report as inadecuate



 Vol 9: Lineage-Specific Regulation of Epigenetic Modifier Genes in Human Liver and Brain.


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This article is from PLoS ONE, volume 9.AbstractDespite 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.



Author: Weng, Matthias K.; Natarajan, Karthick; Scholz, Diana; Ivanova, Violeta N.; Sachinidis, Agapios; Hengstler, Jan G.; Waldmann, Tanja; Leist, Marcel

Source: https://archive.org/







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