
The endpoints of chromatin looped domains (TADs) in Drosophila are determined by a mechanism in which boundary elements physically pair with their partners, rather than by a cohesin-mediated loop extrusion process.


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Two different models have been proposed to explain how the endpoints of chromatin looped domains (“TADs”) in eukaryotic chromosomes are determined. In the first, a cohesin complex extrudes a loop until it encounters a boundary element roadblock, generating a stem-loop. In this model, boundaries are functionally autonomous: they have an intrinsic ability to halt the movement of incoming cohesin complexes that is independent of the properties of neighboring boundaries. In the second, loops are generated by boundary:boundary pairing. In this model, boundaries are functionally non-autonomous, and their ability to form a loop depends upon how well they match with their neighbors. Moreover, unlike the loop-extrusion model, pairing interactions can generate both stem-loops and circle-loops. We have used a combination of MicroC to analyze how TADs are organized, and experimental manipulations of the even skipped TAD boundary, homie , to test the predictions of the “loop-extrusion” and the “boundary-pairing” models. Our findings are incompatible with the loop-extrusion model and instead suggest that the endpoints of TADs in flies are determined by a mechanism in which boundary elements physically pair with their partners, either head-to-head or head-to-tail, with varying degrees of specificity. Although our experiments do not address how partners find each other, the mechanism is unlikely to require loop extrusion.

### Competing Interest Statement

The authors have declared no competing interest.

Chromosome Structure I: Loop extrusion or boundary:boundary pairing?

chromosome-structure-and-looping-insights-from-the-even-skipped-locus-in-drosophila


Chromosome Structure and Looping: Insights from the Even-Skipped Locus in Drosophila
