
다세포 진핵생물의 염색체는 TAD라고 불리는 일련의 위상적으로 독립적인 루프로 구성되어 있다. TAD 경계부는 서로 다른 방향으로 결합하여 줄기 루프 TAD와 원형 루프 TAD를 형성한다. 이러한 루프 토폴로지의 차이는 물리적 및 조절 환경에 영향을 미친다.


coremsg

The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent. Pairing can be head-to-tail or head-to-head. The former generates a stem-loop TAD, while the latter gives a circle-loop TAD. The TAD that encompasses the Drosophila even skipped ( eve ) gene is formed by the head-to-tail pairing of the nhomie and homie boundaries. To explore the relationship between loop topology and the physical and regulatory landscape, we flanked the nhomie boundary region with two attP sites. The attP sites were then used to generate four boundary replacements: λ DNA , nhomie forward (WT orientation), nhomie reverse (opposite of WT orientation), and homie forward (same orientation as WT homie ). The nhomie forward replacement restores the WT physical and regulatory landscape: In MicroC experiments, the eve TAD is a “volcano” triangle topped by a plume, and the eve gene and its regulatory elements are sequestered from interactions with neighbors. The λ DNA replacement lacks boundary function: the endpoint of the “new” eve TAD on the nhomie side is ill-defined, and eve stripe enhancers activate a nearby gene, eIF3j. While nhomie reverse and homie forward restore the eve TAD, the topology is a circle-loop, and this changes the local physical and regulatory landscape. In MicroC experiments, the eve TAD interacts with its neighbors, and the plume at the top of the eve triangle peak is instead flanked by a pair of “clouds” of contacts with the next-door TADs. Consistent with the loss of isolation afforded by the stem-loop topology, the eve enhancers weakly activate genes in the neighboring TADs. Conversely, eve function is partially disrupted.

### Competing Interest Statement

The authors have declared no competing interest.

염색체 구조 II: 줄기 루프와 원형 루프