清华大学刘念团队宣布他们的研究发现染色质调节因子ANKRD11的凝聚物限制高转录基因以保护发育。相关论文发表在2026年7月22日出版的《细胞》杂志上。
使用双层遗传筛选，该研究团队确定了一个调节超转录位点的基因网络，该基因网络在发育障碍中突变的基因中特别丰富。其中，KBG综合征中一种染色质调节因子单倍不足的ANKRD11，对更多高度转录的基因施加越来越强的抑制作用。ANKRD11在高转录位点周围富集，并通过电荷块模式的内在无序区域形成生物分子凝聚体。这些凝聚物在空间上隔离了RNA聚合酶II的延伸因子，从而限制了转录延伸。
在小鼠中，ANKRD11缺失消除了这种限制，导致异常发育基因激活、器官发生中断和胚胎致死。关键的是，具有ANKRD11突变的KBG患者细胞显示有缺陷的凝聚形成和随之而来的高转录基因的过度激活。这些结果揭示了冷凝物介导的限制高转录基因的机制，并表明其破坏是发育障碍（如KBG综合征）的基础。
据了解，定义细胞身份的基因通常是高度转录的，但如何调节它们的活性以防止病理性失调仍然是未知的。
附：英文原文
Title: Condensates of the chromatin regulator ANKRD11 restrict hypertranscribed genes to safeguard development
Author: Tao Zhang, Xiufeng Li, Wei Zhou, Zhao-Lu Li, Jundong Bi, Xin Ma, Xiang Li, Yiming Fan, Yaqiang Hong, Shiqi Wang, Yankun Wang, Le Yang, Yongxing Chen, Wei Qin, Haifeng Wang, Qiaoran Xi, Songhai Shi, Nian Liu
Issue&Volume: 2026-07-22
Abstract: Genes that define cell identity are often highly transcribed, but how their activity is regulated to prevent pathological dysregulation remains elusive. Using a two-tiered genetic screen, we identify a network of genes regulating hypertranscribed loci, which is notably enriched for genes mutated in developmental disorders. Among these, ANKRD11, a chromatin regulator haploinsufficient in KBG syndrome, exerts progressively stronger repression on more highly transcribed genes. ANKRD11 enriches around hypertranscribed loci and forms biomolecular condensates via charge-block-patterned intrinsically disordered regions. These condensates spatially sequester elongation factors away from RNA polymerase II, thereby restricting transcription elongation. In mice, Ankrd11 loss abrogates this restriction, causing aberrant developmental gene activation, disrupted organogenesis, and embryonic lethality. Critically, KBG patient cells with ANKRD11 mutations show defective condensate formation and consequent overactivation of hypertranscribed genes. These results uncover a condensate-mediated mechanism that restricts hypertranscribed genes and suggest its disruption underlies developmental disorders such as KBG syndrome.
DOI: 10.1016/j.cell.2026.07.006
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00804-4