近日，清华大学李寅青等研究人员合作发现，双重作用的转录因子稳定中间表达水平。2024年4月16日，《细胞》杂志在线发表了这项成果。

研究人员利用一系列新开发的测序、成像和功能测定方法，发现了一类具有激活剂和抑制剂双重作用的转录因子，即凝聚形成水平调节的双重作用转录因子（TF）。它们减少高表达，但增加低表达，以达到稳定的中间水平。双重作用转录因子通过凝聚形成结构域直接发挥激活和抑制功能，这些结构域可选择性地分隔核心转录单元。

这些结构域的临床相关突变与一系列发育障碍有关，会损害凝聚物的选择性和双重作用TF的活性。这些结果共同解决了表达调控中的一个基本问题，并证明了水平调控双重作用TF作为工程控制表达水平的强大效应因子的潜力。

据悉，基因表达水平的精确控制对细胞的正常功能至关重要，然而它们是如何定义和严格维持的，尤其是在中间水平，仍然是个谜。

附：英文原文

Title: Dual-role transcription factors stabilize intermediate expression levels

Author: Jinnan He, Xiangru Huo, Gaofeng Pei, Zeran Jia, Yiming Yan, Jiawei Yu, Haozhi Qu, Yunxin Xie, Junsong Yuan, Yuan Zheng, Yanyan Hu, Minglei Shi, Kaiqiang You, Tingting Li, Tianhua Ma, Michael Q. Zhang, Sheng Ding, Pilong Li, Yinqing Li

Issue&Volume: 2024-04-16

Abstract: Precise control of gene expression levels is essential for normal cell functions,yet how they are defined and tightly maintained, particularly at intermediate levels,remains elusive. Here, using a series of newly developed sequencing, imaging, andfunctional assays, we uncover a class of transcription factors with dual roles asactivators and repressors, referred to as condensate-forming level-regulating dual-actiontranscription factors (TFs). They reduce high expression but increase low expressionto achieve stable intermediate levels. Dual-action TFs directly exert activating andrepressing functions via condensate-forming domains that compartmentalize core transcriptionalunit selectively. Clinically relevant mutations in these domains, which are linkedto a range of developmental disorders, impair condensate selectivity and dual-actionTF activity. These results collectively address a fundamental question in expressionregulation and demonstrate the potential of level-regulating dual-action TFs as powerfuleffectors for engineering controlled expression levels.

DOI: 10.1016/j.cell.2024.03.023

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00314-3