美国宾夕法尼亚大学Gerd A. Blobel团队近期取得重要工作进展，他们研究提出，YY1控制的调节连接和转录受细胞周期的影响。相关研究成果2024年8月29日在线发表于《自然—遗传学》杂志上。

据介绍，很少有转录因子在物理连接增强子和启动子中的直接作用被研究。在红细胞中，YY1的急性降解表明，它需要维持许多增强子-启动子环，而不是隔室或结构域。尽管有报道称YY1具有与内聚蛋白相互作用的能力，但YY1依赖性增强子-启动子环的形成并不涉及内聚蛋白介导的环挤出的停滞。

通过整合有丝分裂与G1期动力学，研究人员观察到YY1在有丝分裂染色质上的部分保留，主要是在基因启动子处，然后在有丝分化退出期间快速再结合，与增强子-启动子环的建立相吻合。在有丝分裂到G1期间期，YY1的降解揭示了一组增强子-启动子环，这些环在G1期进入时需要YY1建立，但在间期不需要YY1维持，这表明细胞周期阶段影响YY1的结构功能。

因此，这一研究表明，转录因子的染色质结构功能在与CTCF和内聚蛋白的相互作用以及细胞周期阶段中可能会有所不同。

附：英文原文

Title: YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle

Author: Lam, Jessica C., Aboreden, Nicholas G., Midla, Susannah C., Wang, Siqing, Huang, Anran, Keller, Cheryl A., Giardine, Belinda, Henderson, Kate A., Hardison, Ross C., Zhang, Haoyue, Blobel, Gerd A.

Issue&Volume: 2024-08-29

Abstract: Few transcription factors have been examined for their direct roles in physically connecting enhancers and promoters. Here acute degradation of Yin Yang 1 (YY1) in erythroid cells revealed its requirement for the maintenance of numerous enhancer–promoter loops, but not compartments or domains. Despite its reported ability to interact with cohesin, the formation of YY1-dependent enhancer–promoter loops does not involve stalling of cohesin-mediated loop extrusion. Integrating mitosis-to-G1-phase dynamics, we observed partial retention of YY1 on mitotic chromatin, predominantly at gene promoters, followed by rapid rebinding during mitotic exit, coinciding with enhancer–promoter loop establishment. YY1 degradation during the mitosis-to-G1-phase interval revealed a set of enhancer–promoter loops that require YY1 for establishment during G1-phase entry but not for maintenance in interphase, suggesting that cell cycle stage influences YY1’s architectural function. Thus, as revealed here for YY1, chromatin architectural functions of transcription factors can vary in their interplay with CTCF and cohesin as well as by cell cycle stage.

DOI: 10.1038/s41588-024-01871-y

Source: https://www.nature.com/articles/s41588-024-01871-y