spatial proximity and similarity of the epigenetic state of genome domains空间距离和相似性的基因组的表观遗传状态域.pdf

Spatial Proximity and Similarity of the Epigenetic State of Genome Domains 1,2 1,2 1 3,4 Ekaterina E. Khrameeva *, Andrey A. Mironov , Gennady G. Fedonin , Philipp Khaitovich , Mikhail S. Gelfand1,2 1 Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia, 2 Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia, 3 Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai, China, 4 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany Abstract Recent studies demonstrate that the organization of the chromatin within the nuclear space might play a crucial role in the regulation of gene expression. The ongoing progress in determination of the 3D structure of the nuclear chromatin allows one to study correlations between spatial proximity of genome domains and their epigenetic state. We combined the data on three-dimensional architecture of the whole human genome with results of high-throughput studies of the chromatin functional state and observed that fragments of different chromosomes that are spatially close tend to have similar patterns of histone modifications, methylation state, DNAse sensitivity, expression level, and chromatin states in general. Moreover, clustering of genome regions by spatial proximity produced compact clusters characterized by the high level of histone modifications and DNAse sensitivity and low methylation level, and loose clusters with the opposite characteristics. We also associated the spatial proximity data with previously detected chimeric transcripts and the results of RNA-seq experiments and