A network biology approach to epigenetic regulation

author: Alfonso Valencia, Spanish National Cancer Research Centre (CNIO)
published: July 18, 2016,   recorded: May 2016,   views: 1096


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The description of molecular systems as networks opens the possibility of using all the methodology developed for network analysis in other fields from sociology to neurology. In this case, we have analysed the properties of Mouse Embryonic Stem Cells (mESC) at different levels of the organization of epigenetic modifications. mESC is currently the best characterised epigenetics system, including data on many of the basic components: Chromatin Related Proteins (CRPs), Histone modifications, DNA methylation modifications, the genome mapping preferences of a large collection of proteins and modifications (ChIP-Seq data) and organization of the chromatin in the nucleus, determined with Chromatin Capture Experiments.

We have processed these heterogeneous “mESC Epigenetic Properties” to build a comprehensive network of CRPs, histone marks and DNA modifications linked by their propensity to co-localize in the genome. In this network co-localization preferences are specific of “mESC Chromatin States”, such as Promoters and Enhancers. The analysis of the properties of the “co-localization” network points to one of the DNA modifications 5hmC as the key component in the organization of this network. The importance of 5hmC in the network is reinforced by the evolutionary analysis of the protein components of the network, in which 5hmC acts as a mediator in the co-evolution of the protein components of the mESC network.

We have further explored the functional significance of the “mESC Epigenetic Properties” and “mESC Chromatin States” by analysing them in the context of the structure of the nucleus that ultimately controls genes expression. The results revealed interesting properties of the organization of the mESC epigenetic control system, in line with the emerging models of gene expression control and chromatin organization. At the methodological level, I will introduce the growing importance of Network analysis methodology in the exploration of the functional and evolutionary properties of complex biological systems.

Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs. Perner et al., (2016) Cell Rep. http://www.cell.com/cell-reports/pdf/S2211-1247(16)00028-0.pdf

Chromatin assortativity: integrating epigenomic data and 3D genomic structure. Pancaldi et al., (2016) http://arxiv.org/abs/1512.00268

This work was developed in collaboration with the Vingron's (MPIMG, Berlin) and Fraser’s (Babraham Institute) labs, and it was financed in part by the BLUEPRINT consortium (http://www.blueprintepigenome.eu)

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