Set7 mediated interactions regulate transcriptional networks in embryonic stem cells

Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell d...

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Autores principales: Tuano, Natasha K., Okabe, Jun, Ziemann, Mark, Cooper, Mark E., El-Osta, Assam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Gene regulation, Chromatin and Epigenetics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100561/
https://www.ncbi.nlm.nih.gov/pubmed/27439711
http://dx.doi.org/10.1093/nar/gkw621
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author Tuano, Natasha K.
Okabe, Jun
Ziemann, Mark
Cooper, Mark E.
El-Osta, Assam
author_facet Tuano, Natasha K.
Okabe, Jun
Ziemann, Mark
Cooper, Mark E.
El-Osta, Assam
author_sort Tuano, Natasha K.
collection PubMed
description Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells.
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spelling pubmed-51005612016-11-10 Set7 mediated interactions regulate transcriptional networks in embryonic stem cells Tuano, Natasha K. Okabe, Jun Ziemann, Mark Cooper, Mark E. El-Osta, Assam Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells. Oxford University Press 2016-11-02 2016-07-20 /pmc/articles/PMC5100561/ /pubmed/27439711 http://dx.doi.org/10.1093/nar/gkw621 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Tuano, Natasha K.
Okabe, Jun
Ziemann, Mark
Cooper, Mark E.
El-Osta, Assam
Set7 mediated interactions regulate transcriptional networks in embryonic stem cells
title Set7 mediated interactions regulate transcriptional networks in embryonic stem cells
title_full Set7 mediated interactions regulate transcriptional networks in embryonic stem cells
title_fullStr Set7 mediated interactions regulate transcriptional networks in embryonic stem cells
title_full_unstemmed Set7 mediated interactions regulate transcriptional networks in embryonic stem cells
title_short Set7 mediated interactions regulate transcriptional networks in embryonic stem cells
title_sort set7 mediated interactions regulate transcriptional networks in embryonic stem cells
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100561/
https://www.ncbi.nlm.nih.gov/pubmed/27439711
http://dx.doi.org/10.1093/nar/gkw621
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AT coopermarke set7mediatedinteractionsregulatetranscriptionalnetworksinembryonicstemcells
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