Hbo1和Msl复合体在有丝分裂过程中保持了活性和非活性X染色体的差异压实和H3K27me3标记，这一成果由牛津大学Amanda G. Fisher研究组经过不懈努力而取得。相关论文于2025年9月8日发表在《自然—细胞生物学》杂志上。

在这里，该课题组人员展示了主题染色体流分选，在有丝分裂期间，Xist相关蛋白从无活性X（Xi）染色体上分离，而高水平的H3K27me3和相对于活性X（Xa）增加的Xi压实被保留。有丝分裂Xi和Xa的蛋白质组学比较显示，与Xi和常染色体相比，Xa上Hbo1和Msl/Mof组蛋白乙酰转移酶复合物的成分显著富集。相反，组蛋白乙酰化抑制剂与Xi共富集。

此外，抑制Hbo1或删除Msl/Mof成分从功能上消除了H3K27me3标记和染色体压实的有丝分裂差异。这些数据揭示了乙酰化途径在有丝分裂期间保存X染色体特性中的关键作用。

研究人员表示，在哺乳动物中，全染色体调节机制确保雄性（XY）和雌性（XX）之间x连锁基因剂量的平衡。在雌性细胞中，来自两条X染色体之一的基因表达减少，在整个间期观察到Xist-RNA、Xist -相关蛋白、特异性组蛋白修饰（例如H3K27me3）和Barr体形成的选择性积累。

附：英文原文

Title: Hbo1 and Msl complexes preserve differential compaction and H3K27me3 marking of active and inactive X chromosomes during mitosis

Author: Djeghloul, Dounia, Cheriyamkunnel, Sherry, Patel, Bhavik, Kramer, Holger, Montoya, Alex, Brown, Karen E., Whilding, Chad, Nesterova, Tatyana B., Wei, Guifeng, Brockdorff, Neil, Grzdzielewska, Iga, Karayol, Remzi, Akhtar, Asifa, Merkenschlager, Matthias, Fisher, Amanda G.

Issue&Volume: 2025-09-08

Abstract: In mammals, chromosome-wide regulatory mechanisms ensure a balance of X-linked gene dosage between males (XY) and females (XX). In female cells, expression of genes from one of the two X chromosomes is curtailed, with selective accumulation of Xist-RNA, Xist-associated proteins, specific histone modifications (for example, H3K27me3) and Barr body formation observed throughout interphase. Here we show, using chromosome flow-sorting, that during mitosis, Xist-associated proteins dissociate from inactive X (Xi) chromosomes, while high levels of H3K27me3 and increased compaction of the Xi relative to active X (Xa), are retained. Proteomic comparison of mitotic Xi and Xa revealed that components of Hbo1 and Msl/Mof histone acetyltransferase complexes are significantly enriched on Xa as compared to Xi and autosomes. By contrast, inhibitors of histone acetylation co-enrich with Xi. Furthermore, inhibition of Hbo1 or deletion of Msl/Mof components functionally abolishes mitotic differences in H3K27me3 marking and chromosome compaction. These data uncover critical roles for acetylation pathways in preserving X chromosome properties during mitosis.

DOI: 10.1038/s41556-025-01748-0

Source: https://www.nature.com/articles/s41556-025-01748-0