The Third Level of Genome Functioning: Chromatin Folding

Abstract

Recent experiments have provided us with extensive amount of data which all suggest that chromatin folding is achieved by formation of chromatin-chromatin loops. This observed looping is highly dynamic and linked to cell differentiation. We propose that the chromatin folding constitutes a third level of genome functioning on top of the individual genes and their epigenetic control.Our interest is to study the principles of chromatin folding in the cell nucleus, above all how does chromatin folding relate to gene expression. In this we focus on the molecular mechanisms of formation of loops, dynamics and ergodicity of looping as well as to relation of dynamic looping to genome function.Our experimental approach relies on three-dimensional cell imaging to map the in vivo folding state of chromatin. For the interpretation of our data we use polymer-physics models. The most recent work of our group shows that chromatin folding status is different in genomic regions with higher transcription levels and in transcriptionally silent regions. In both cases the data can be fitted to a random loop polymer model(1).1. Mateos-Langerak, J., Bohn, M., de Leeuw, W., Giromus, O., Manders, E.M.M., Verschure, P. J., Indemanns, M.H.G., Gierman, H.J., Heermann, D.W., van Driel, R., Goetze, S. 2009. Spatially confined folding of chromatin in the interphase nucleus. Proc Natl Acad Sci U S A. 106:3812-7.