The Topologically Associated Domains (TADs) of a Chromatin Correlated with Isochores Organization of a Genome

Background: Recent studies suggest that the one-dimensional genomic feature, isochore, underlie the three-dimensional chromatin architecture. It has also been reported that open chromatin fibers originate from regions of high gene density while closed chromatin corresponds to low gene density chromosomal regions. Objective: To verify how the 3D architecture of chromatin is linked to the one-dimensional genomic features, we analyzed the degree of overlapping between the segments of isochores and TADs of Drosophila melanogaster. Method: Using an R program, we measured the percentage overlapping between the segments of isochores and TADs of 2L, 2R, 3L, 3R and X chromosomes of Drosophila melanogaster and performed a Monte Carlo randomization test to check whether the observed overlapping results are by chance alone or not. Results: The overlapping ratio between the two genomic features was ranged from 71.82% in X chromosome to 79.06% in the 2R chromosome when the ranges of TADs were mapped onto isochores and 66.97% in X chromosome to 74.14% in chromosome 2R when the ranges of isochores were mapped onto TAD ranges in D. melanogaster. Conclusion: The probability test on 1000 random samples for each chromosome demonstrated that there exists a statistically significant correlation between the isochores and TADs (at FDR of 0.05) that could not be obtained by chance alone. In general, this finding would have an interesting implication in deducing the 3D structure of a chromatin from the isochores organization, especially in genomes that lack TADs.