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Epigenomes 2018, 2(4), 20; https://doi.org/10.3390/epigenomes2040020

On the Cooperation between Epigenetics and Transcription Factor Networks in the Specification of Tissue Stem Cells

1
Interdisciplinary Centre for Bioinformatics, University Leipzig, Haertelstr. 16-18, 04107 Leipzig, Germany
2
Department of Surgery, Research Laboratories, University Leipzig, Liebigstr. 19, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 15 September 2018 / Revised: 12 October 2018 / Accepted: 18 October 2018 / Published: 23 October 2018
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Abstract

It is generally accepted that epigenetic modifications, such as DNA and histone methylations, affect transcription and that a gene’s transcription feeds back on its epigenetic profile. Depending on the epigenetic modification, positive and negative feedback loops have been described. Here, we study whether such interrelation are mandatory and how transcription factor networks affect it. We apply self-organizing map machine learning to a published data set on the specification and differentiation of murine intestinal stem cells in order to provide an integrative view of gene transcription and DNA, as well as histone methylation during this process. We show that, although gain/loss of H3K4me3 at a gene promoter is generally considered to be associated with its increased/decreased transcriptional activity, such an interrelation is not mandatory, i.e., changes of the modification level do not necessarily affect transcription. Similar considerations hold for H3K27me3. In addition, even strong changes in the transcription of a gene do not necessarily affect its H3K4me3 and H3K27me3 modification profile. We provide a mechanistic explanation of these phenomena that is based on a model of epigenetic regulation of transcription. Thereby, the analyzed data suggest a broad variance in gene specific regulation of histone methylation and support the assumption of an independent regulation of transcription by histone methylation and transcription factor networks. The results provide insights into basic principles of the specification of tissue stem cells and highlight open questions about a mechanistic modeling of this process. View Full-Text
Keywords: epigenetic regulation; transcription; H3K4me3; H3K27me3; mathematical model; self-organizing map; intestinal stem cell specification epigenetic regulation; transcription; H3K4me3; H3K27me3; mathematical model; self-organizing map; intestinal stem cell specification
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Thalheim, T.; Hopp, L.; Binder, H.; Aust, G.; Galle, J. On the Cooperation between Epigenetics and Transcription Factor Networks in the Specification of Tissue Stem Cells. Epigenomes 2018, 2, 20.

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