In search of structure-function connections in chromatin at multiple lengths scales
In enzymes, structure uniquely determines function, but in chromatin, the relationship is likely more complex. At the level of the nucleosome, we use a multi-state atomistic model to explore virtually all possible charge-altering post-translational modifications (PTMs) in the globular histone core. The model reveals a rich and nuanced picture: the effect of PTMs varies greatly depending on location, including counter-intuitive trends such as decrease of DNA accessibility for some lysine acetylations in the core. A connection to transcription regulation in-vivo is made; unexpectedly high sensitivity to small variations of intra-nuclear pH is predicted. At the level of the whole nucleus (fruit fly), we combine a coarse-grained dynamic model with genome-wide gene expression data to look for a connection between positioning of genes at nuclear periphery and their expression level. Our findings suggest that the stochastic positioning of topologically associating domains (TADs) at the nuclear envelope does not, by itself, systematically affect the mean level of gene expression in these TADs, while a very weak negative correlation is confirmed.