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Int. J. Mol. Sci. 2017, 18(5), 1069; doi:10.3390/ijms18051069

The Regulatory Capacity of Bivalent Genes—A Theoretical Approach

1
Interdisciplinary Centre for Bioinformatics, University Leipzig, Haertelstr. 16-18, 04107 Leipzig, Germany
2
Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Haertelstr. 16-18, 04107 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Nicoletta Sacchi
Received: 3 April 2017 / Revised: 8 May 2017 / Accepted: 10 May 2017 / Published: 17 May 2017
(This article belongs to the Special Issue Cancer Epigenetics)
View Full-Text   |   Download PDF [6534 KB, uploaded 17 May 2017]   |  

Abstract

Bivalent genes are frequently associated with developmental and lineage specification processes. Resolving their bivalency enables fast changes in their expression, which potentially can trigger cell fate decisions. Here, we provide a theoretical model of bivalency that allows for predictions on the occurrence, stability and regulatory capacity of this prominent modification state. We suggest that bivalency enables balanced gene expression heterogeneity that constitutes a prerequisite of robust lineage priming in somatic stem cells. Moreover, we demonstrate that interactions between the histone and DNA methylation machineries together with the proliferation activity control the stability of the bivalent state and can turn it into an unmodified state. We suggest that deregulation of these interactions underlies cell transformation processes as associated with acute myeloid leukemia (AML) and provide a model of AML blast formation following deregulation of the Ten-eleven Translocation (TET) pathway. View Full-Text
Keywords: bivalent gene; histone modification; gene expression heterogeneity; lineage specification; aberrant DNA methylation; blast formation bivalent gene; histone modification; gene expression heterogeneity; lineage specification; aberrant DNA methylation; blast formation
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Thalheim, T.; Herberg, M.; Loeffler, M.; Galle, J. The Regulatory Capacity of Bivalent Genes—A Theoretical Approach. Int. J. Mol. Sci. 2017, 18, 1069.

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