Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Modeling the regulation of bivalent genes
Joerg Galle, Jens Przybilla

Last modified: 2014-03-31


Bivalent genes are genes the associated nucleosomes of which carry trimethylation of both lysine 4 and 27 of histone 3 (H3K4me3/H3K27me3). They have been demonstrated to be involved in controlling many developmental and differentiation processes. During these processes the bivalent state of the genes resolves either into a transcription activating, pure H3K4me3 or a repressive, pure H3K27me3 state.

In the last years experimental studies have provided detailed insights into molecular level interaction between the enzymes setting these chromatin modifications and the DNA as well as between the enzymes and DNA-methyltransferases. These results led us to develop a biophysical model of the regulation of bivalent genes by binding of transcription factors to their promoters and of chromatin modifying enzymes to the associated chromatin. 

Here, we analyze the impact of the co-operativity of these binding events onto the transcriptional activity of the genes and demonstrate that limited inheritance of both involved histone modifications can induce genome-wide regulatory changes during cell proliferation. Our model provides a mechanistic explanation why hyper-methylation of gene promoters during malignant cell transformation is observed in genes the associated nucleosomes of which carry H3K27me3.

Our approach represents a basic step towards a better understanding of the epigenetic regulation of developmental and differentiation processes as well as of the epigenetic response to malignant transformation.   


epigenetics; histone modifications; DNA hyper-methylation