In situdissection of domain boundaries affect genome topology and gene transcription inDrosophila

Abstract

26The molecular mechanisms responsible for Topologically Associated Domains (TADs) 27 formation are not yet fully understood. In Drosophila, it has been proposed that 28 transcription is fundamental for TAD organization while the participation of genetic 29 sequences bound by Architectural Proteins (APs) remains controversial. Here, we 30 investigate the contribution of domain boundaries to TAD organization and the regulation 31 of gene expression at the Notch gene locus in Drosophila. We find that deletion of domain 32 boundaries results in TAD fusion and long-range topological defects that are accompanied 33 by loss of APs and RNA Pol II chromatin binding as well as defects in transcription. 34 Together, our results provide compelling evidence on the contribution of discrete genetic 35 sequences bound by APs and RNA Pol II in the partition of the genome into TADs and in 36 the regulation of gene expression in Drosophila. 37 38