宾夕法尼亚大学Gerd A. Blobel小组研究出在没有NIPBL驱动的染色质环挤压的情况下，顺式调节接触的从头形成。2026年4月13日，国际知名学术期刊《自然—遗传学》发表了这一成果。

为了解决这个问题，研究小组描述了NIPBL缺失细胞在有丝分裂到G1期转变过程中结构环和CRE环的形成。结构环的形成与环长成正比。计算模型支持这些观察结果，表明NIPBL促进了黏结蛋白加载和萃取。值得注意的是，大多数CRE环，无论长度如何，都是在NIPBL降解后正常建立的。虽然在NIPBL缺失的细胞中，弱CRE之间的一部分接触是通过延迟动力学形成的，但通常基因激活仅轻度受损。总的来说，他们的发现表明，有丝分裂后的调控接触和基因转录的建立可以独立于染色质环的外旋而发生。

据了解，NIPBL通过内聚蛋白复合物促进染色质环外移，直到它在趋同取向的CTCF位点停止，形成结构环。虽然大部分连接顺式调控元件（CRE）的环可以在内聚蛋白缺失的细胞中维持，但环的提取过程是否有助于CRE环的重新建立尚不清楚。

附：英文原文

Title: De novo formation of cis-regulatory contacts in the absence of NIPBL-driven chromatin loop extrusion

Author: Aboreden, Nicholas G., Zhao, Han, Yang, Jin H., Shan, Fengnian, Liu, Fuhai, Hansen, Anders S., Zhang, Haoyue, Blobel, Gerd A.

Issue&Volume: 2026-04-13

Abstract: NIPBL promotes chromatin loop extrusion by the cohesin complex until it stalls at convergently oriented CTCF sites, forming structural loops. While a large fraction of loops connecting cis-regulatory elements (CREs) can be maintained in cohesin-depleted cells, whether the loop extrusion process contributes to the de novo establishment of CRE loops remains unclear. To address this question, we characterized the formation of structural and CRE loops in NIPBL-depleted cells during the mitosis-to-G1-phase transition. Structural loop formation was impaired proportionally to loop length. Computational modeling supports these observations, suggesting that NIPBL promotes both cohesin loading and extrusion. Notably, most CRE loops, regardless of length, were established normally upon NIPBL degradation. While a subset of contacts among weak CREs were formed with delayed kinetics in NIPBL-depleted cells, generally gene activation was only mildly impaired. Collectively, our findings suggest that postmitotic establishment of regulatory contacts and gene transcription can occur independently of chromatin loop extrusion.

DOI: 10.1038/s41588-026-02565-3

Source: https://www.nature.com/articles/s41588-026-02565-3