Universität zu Köln

Weng, Matthias K., Natarajan, Karthick, Scholz, Diana, Ivanova, Violeta N., Sachinidis, Agapios, Hengstler, Jan G., Waldmann, Tanja and Leist, Marcel ORCID: 0000-0002-3778-8693 (2014). Lineage-Specific Regulation of Epigenetic Modifier Genes in Human Liver and Brain. PLoS One, 9 (7). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weng, Matthias K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Natarajan, Karthick UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Ivanova, Violeta N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Hengstler, Jan G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldmann, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-433759
DOI:	10.1371/journal.pone.0102035
Journal or Publication Title:	PLoS One
Volume:	9
Number:	7
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-CYCLE REGULATION; CHROMATIN MODIFICATIONS; RETINOBLASTOMA PROTEIN; HISTONE MODIFICATIONS; ALZHEIMERS-DISEASE; MAMMALIAN-CELLS; STEM-CELLS; EXPRESSION; MECHANISMS; ACETYLATION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43375