Lineage-specific regulation of epigenetic modifier genes in human liver and brain.

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...

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Autores principales:	Matthias K Weng, Karthick Natarajan, Diana Scholz, Violeta N Ivanova, Agapios Sachinidis, Jan G Hengstler, Tanja Waldmann, Marcel Leist
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f5f91f2d5d7442459ed07ae99b11c5bf
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spelling	oai:doaj.org-article:f5f91f2d5d7442459ed07ae99b11c5bf2021-11-25T06:07:28ZLineage-specific regulation of epigenetic modifier genes in human liver and brain.1932-620310.1371/journal.pone.0102035https://doaj.org/article/f5f91f2d5d7442459ed07ae99b11c5bf2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25054330/?tool=EBIhttps://doaj.org/toc/1932-6203Despite 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.Matthias K WengKarthick NatarajanDiana ScholzVioleta N IvanovaAgapios SachinidisJan G HengstlerTanja WaldmannMarcel LeistPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e102035 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthias K Weng Karthick Natarajan Diana Scholz Violeta N Ivanova Agapios Sachinidis Jan G Hengstler Tanja Waldmann Marcel Leist Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
description	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.
format	article
author	Matthias K Weng Karthick Natarajan Diana Scholz Violeta N Ivanova Agapios Sachinidis Jan G Hengstler Tanja Waldmann Marcel Leist
author_facet	Matthias K Weng Karthick Natarajan Diana Scholz Violeta N Ivanova Agapios Sachinidis Jan G Hengstler Tanja Waldmann Marcel Leist
author_sort	Matthias K Weng
title	Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
title_short	Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
title_full	Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
title_fullStr	Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
title_full_unstemmed	Lineage-specific regulation of epigenetic modifier genes in human liver and brain.
title_sort	lineage-specific regulation of epigenetic modifier genes in human liver and brain.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f5f91f2d5d7442459ed07ae99b11c5bf
work_keys_str_mv	AT matthiaskweng lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT karthicknatarajan lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT dianascholz lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT violetanivanova lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT agapiossachinidis lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT janghengstler lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT tanjawaldmann lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain AT marcelleist lineagespecificregulationofepigeneticmodifiergenesinhumanliverandbrain
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Lineage-specific regulation of epigenetic modifier genes in human liver and brain.

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