The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension.
The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension.
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DOI：
10.1016/j.cell.2017.04.013
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发表时间：
2017-05-04
期刊：
影响因子：
64.5
通讯作者：
Rowland BD
中科院分区：
文献类型：
--
作者：
Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
染色体的空间组织影响包括基因表达在内的许多核过程。内聚蛋白复合体通过沿染色体将CTCF位点环在一起形成三维基因组。我们在这里展示了染色质环的大小可以增加，并且内聚蛋白拥抱DNA的持续时间决定了环扩大的程度。内聚蛋白的DNA释放因子WAPL限制了这种环的延伸，也阻止了错误定向的CTCF位点之间的环。我们发现SCC2/SCC4复合体促进染色质环的延伸和拓扑相关结构域（TADs）的形成。我们的数据支持黏结蛋白通过环的不断扩大来构建染色体的模型，并且TADs反映了正在形成的环的多克隆集合。最后，我们发现虽然内聚蛋白促进染色体环，但它限制了核区隔化。我们得出结论，SCC2/SCC4和WAPL的平衡活性使内聚蛋白能够正确地构建染色体。Hi-C分析表明，染色质环的长度可以在全基因组范围内增加，内聚蛋白包围DNA的持续时间决定了染色质环的长度，单倍体遗传学揭示SCC2/SCC4复合体促进了环的延伸，内聚蛋白限制了细胞核内染色质的区隔化，内聚蛋白与DNA的动态关联决定了染色质环的长度，并允许该复合体正确地结构染色体。
The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes. Hi-C analysis demonstrates that chromatin loop size can be increased genome-wide The duration with which cohesin embraces DNA determines the length of chromatin loops Haploid genetics reveals that the SCC2/SCC4 complex promotes loop extension Cohesin limits the compartmentalization of chromatin within the nucleus Cohesin's dynamic association with DNA determines the length of chromatin loops and allows this complex to correctly structure chromosomes.