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Shared binding sites for the chromosomal architectural protein Su(Hw) mediate physical interactions between Drosophila TAD boundaries

ABSTRACT: The canonical insulator/boundary element binding protein in Drosophila, Su(Hw), originally identified via its function in the gypsy transposable element, has been suggested to have a role in a large fraction of boundaries throughout the genome. Its functional role has been established in a variety of genetic phenomena that are thought to depend on boundary pairing interactions. However, molecular models of its pairing function remain incomplete. Here we show that it functions in both of the boundaries that flank the even skipped locus, homie and nhomie, and that it specifically mediates both long-range cis and trans interactions between these two elements. While it is a crucial part of the function of these two boundaries, which pair with each other specifically and in one preferred orientation, it is not sufficient to account for either their specificity of function or the strength of their pairing. The effects of removing it in either homie or nhomie on gene expression that is mediated by their pairing function is precisely mirrored in the corresponding physical interactions between the elements. The details of these effects confirm our previous model of how boundaries pair in Drosophila, and are inconsistent with models of TAD formation mediated by loop extrusion. These studies also show that gene expression induced by bridging between distant boundaries is subject to a complex set of trade-offs between pairing specificity and promiscuity, and that these complexities can be largely, but perhaps not fully, accounted for by the effects on physical pairing interactions, as revealed by MicroC assays.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE330020 | GEO | 2026/05/26

REPOSITORIES: GEO

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Stem-loop and circle-loop TADs generated by directional pairing of boundary elements have distinct physical and regulatory properties

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