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Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis

BACKGROUND: Epigenetic mechanisms regulate gene expression patterns affecting cell function and differentiation. In this report, we examine the role of histone acetylation in gene expression regulation in mouse embryonic stem cells employing transcriptomic and epigenetic analysis. RESULTS: Embryonic...

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Autores principales: Karantzali, Efthimia, Schulz, Herbert, Hummel, Oliver, Hubner, Norbert, Hatzopoulos, AK, Kretsovali, Androniki
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643936/
https://www.ncbi.nlm.nih.gov/pubmed/18394158
http://dx.doi.org/10.1186/gb-2008-9-4-r65
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author Karantzali, Efthimia
Schulz, Herbert
Hummel, Oliver
Hubner, Norbert
Hatzopoulos, AK
Kretsovali, Androniki
author_facet Karantzali, Efthimia
Schulz, Herbert
Hummel, Oliver
Hubner, Norbert
Hatzopoulos, AK
Kretsovali, Androniki
author_sort Karantzali, Efthimia
collection PubMed
description BACKGROUND: Epigenetic mechanisms regulate gene expression patterns affecting cell function and differentiation. In this report, we examine the role of histone acetylation in gene expression regulation in mouse embryonic stem cells employing transcriptomic and epigenetic analysis. RESULTS: Embryonic stem cells treated with the histone deacetylase inhibitor Trichostatin A (TSA), undergo morphological and gene expression changes indicative of differentiation. Gene profiling utilizing Affymetrix microarrays revealed the suppression of important pluripotency factors, including Nanog, a master regulator of stem cell identity, and the activation of differentiation-related genes. Transcriptional and epigenetic changes induced after 6-12 hours of TSA treatment mimic those that appear during embryoid body differentiation. We show here that the early steps of stem cell differentiation are marked by the enhancement of bulk activatory histone modifications. At the individual gene level, we found that transcriptional reprogramming triggered by histone deacetylase inhibition correlates with rapid changes in activating K4 trimethylation and repressive K27 trimethylation of histone H3. The establishment of H3K27 trimethylation is required for stable gene suppression whereas in its absence, genes can be reactivated upon TSA removal. CONCLUSION: Our data suggest that inhibition of histone deacetylases accelerates the early events of differentiation by regulating the expression of pluripotency- and differentiation-associated genes in an opposite manner. This analysis provides information about genes that are important for embryonic stem cell function and the epigenetic mechanisms that regulate their expression.
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spelling pubmed-26439362009-02-17 Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis Karantzali, Efthimia Schulz, Herbert Hummel, Oliver Hubner, Norbert Hatzopoulos, AK Kretsovali, Androniki Genome Biol Research BACKGROUND: Epigenetic mechanisms regulate gene expression patterns affecting cell function and differentiation. In this report, we examine the role of histone acetylation in gene expression regulation in mouse embryonic stem cells employing transcriptomic and epigenetic analysis. RESULTS: Embryonic stem cells treated with the histone deacetylase inhibitor Trichostatin A (TSA), undergo morphological and gene expression changes indicative of differentiation. Gene profiling utilizing Affymetrix microarrays revealed the suppression of important pluripotency factors, including Nanog, a master regulator of stem cell identity, and the activation of differentiation-related genes. Transcriptional and epigenetic changes induced after 6-12 hours of TSA treatment mimic those that appear during embryoid body differentiation. We show here that the early steps of stem cell differentiation are marked by the enhancement of bulk activatory histone modifications. At the individual gene level, we found that transcriptional reprogramming triggered by histone deacetylase inhibition correlates with rapid changes in activating K4 trimethylation and repressive K27 trimethylation of histone H3. The establishment of H3K27 trimethylation is required for stable gene suppression whereas in its absence, genes can be reactivated upon TSA removal. CONCLUSION: Our data suggest that inhibition of histone deacetylases accelerates the early events of differentiation by regulating the expression of pluripotency- and differentiation-associated genes in an opposite manner. This analysis provides information about genes that are important for embryonic stem cell function and the epigenetic mechanisms that regulate their expression. BioMed Central 2008-04-04 /pmc/articles/PMC2643936/ /pubmed/18394158 http://dx.doi.org/10.1186/gb-2008-9-4-r65 Text en Copyright © 2008 Karantzali et al.; licensee BioMed Central Ltd. https://creativecommons.org/licenses/by/2.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 (https://creativecommons.org/licenses/by/2.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Karantzali, Efthimia
Schulz, Herbert
Hummel, Oliver
Hubner, Norbert
Hatzopoulos, AK
Kretsovali, Androniki
Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
title Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
title_full Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
title_fullStr Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
title_full_unstemmed Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
title_short Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
title_sort histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643936/
https://www.ncbi.nlm.nih.gov/pubmed/18394158
http://dx.doi.org/10.1186/gb-2008-9-4-r65
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