SRA

The DNA in humans and many animals is compartmentalised in topologically associating domains (TADs). In Drosophila, several architectural proteins are enriched at TAD borders, but we are still missing evidence that these proteins have a functional role in TAD maintenance. Here, we show that depletion of BEAF-32, Cp190 and Chro leads to changes in TAD organisation and chromatin loops. Their depletion affects mainly TAD borders in heterochromatin, while euchromatin TAD borders are resilient to these mutants. Furthermore, transcriptomic data identified thousands of genes displaying differential expression in these mutants and that majority of differentially expressed genes are in TADs that are reorganised. In contrast, we observed a lower effect on gene expression by the loss of chromatin loops. Our work identified for the first time a functional role for architectural proteins at TAD borders in Drosophila and a strong link between TAD reorganisation and changes in gene expression. Overall design: Comparison of Hi-C and RNA-seq data in WT and mutant (BEAF-32; Cp190 and Chro; BEAF-32 and Dref) Drosophila melanogaster cell lines BG3 (derived from larval central nervous system)