Changes of Chromatin 3D-structure in Embryogenesis

The three-dimensional structure of the Drosophila chromatin has been shown to change at the early stages of embryogenesis from the state with no local structures to compartmentalized chromatin segregated into topologically associated domains (TADs). It was established that TAD borders appears during the early ebryogenesis in the loci enriched with housekeeping genes and epigenetic signal. However, the insulation dynamics of TAD borders and its association with the expression and epigenetics dynamics is not fully understood. As TAD borders calling and analysis of TAD borders dynamics have no standard, universally accepted solution, we have developed and implemented in our tool HiChew an algorithm to find an optimal annotation of TAD borders given an expected size of TADs for subsequent clustering of TAD borders based on their insulation dynamics during the embryogenesis. To validate the approach, we demonstrate that insulation dynamics in HiChew clusters correlate with genomic and epigenomic characteristics. Particularly, in accordance with previous findings, the insulation rate of TAD borders is positively correlated with the housekeeping genes enrichment in borders loci. We also report that insulation rate of TAD borders is associated with the enrichment of epigenetic ATAC-Seq signal and DNase I hypersensitive sites in the loci of these borders.