Spindlin1 (SPIN1) 是一种独特的多价组蛋白修饰读取器，在核糖体 RNA 转录、染色体分离和肿瘤发生中发挥作用。然而，SPIN1 N 末端延伸区域的功能仍不清楚。在这里，我们发现SPIN1可以通过其N端本质无序区域（IDR）在体外和体内形成相分离和液体状的冷凝物。 SPIN1 的相分离将组蛋白甲基转移酶 MLL1 募集至相同的缩合物并富集 H3K4 甲基化标记。该过程还促进 SPIN1 与 H3K4me3 的结合并激活肿瘤发生相关基因。此外，SPIN1-IDR 增强了 SPIN1 的全基因组染色质结合，并促进其定位到与 MAPK 信号通路相关的基因。这些发现为 IDR 在调节 SPIN1 活性中的生物学功能提供了新的见解，并揭示了 SPIN1-IDR 在组蛋白甲基化读出中以前未被认识的作用。我们的研究揭示了 SPIN1 适当的生物物理特性在促进基因表达并将相分离与肿瘤发生联系起来的关键作用，这为理解 SPIN1 的功能提供了新的视角。© 作者 2024。由牛津大学出版社代表出版中国科学院上海生命科学研究院生物化学与细胞生物学研究所.

Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.© The Author(s) 2024. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.