中国科学院生物物理研究所朱冰小组发现，靶向非连续着丝粒周围基序以启动异染色质形成。相关论文于2024年7月3日在线发表于国际学术期刊《自然》。

研究人员发现锌指蛋白ZNF512和ZNF512B通过直接结合DNA，特异性定位于着丝粒周围区域。值得注意的是，ZNF512和ZNF512B均足以在异位靶向的重复区域和着丝粒周围区域启动新的异染色质形成，因为它们直接招募SUV39H1和SUV39H2（SUV39H）催化H3K9甲基化。SUV39H2对H3K9三甲基化的贡献更大，而SUV39H1似乎对沉默贡献更多，可能由于其与HP1蛋白的优先结合。

来自不同物种的ZNF512和ZNF512B可以特异性靶向其他脊椎动物的着丝粒周围区域，因为ZNF512和ZNF512B锌指之间的非典型长连接残基在识别每个锌指靶向的非连续排列的三个核苷酸三联体时提供了灵活性。这项研究解答了两个长期存在的问题：如何启动结构性异染色质以及看似可变的着丝粒周围序列如何被脊椎动物中相同的保守机制靶向。

据介绍，着丝粒周围异染色质是染色体的重要组成部分，以组蛋白H3K9（H3K9）甲基化为标志。然而，在脊椎动物中，是什么将H3K9特异性组蛋白甲基转移酶招募到着丝粒周围区域仍不清楚，不同物种的着丝粒周围区域尽管缺乏高度保守的DNA序列，却为何共享相同的H3K9甲基化标志也未解明。

附：英文原文

Title: Targeting pericentric non-consecutive motifs for heterochromatin initiation

Author: Ma, Runze, Zhang, Yan, Zhang, Jing, Zhang, Pinqi, Liu, Zeqi, Fan, Yiming, Wang, Hao-Tian, Zhang, Zhuqiang, Zhu, Bing

Issue&Volume: 2024-07-03

Abstract: Pericentric heterochromatin is a critical component of chromosomes marked by histone H3 K9 (H3K9) methylation1,2,3. However, what recruits H3K9-specific histone methyltransferases to pericentric regions in vertebrates remains unclear4, as does why pericentric regions in different species share the same H3K9 methylation mark despite lacking highly conserved DNA sequences2,5. Here we show that zinc-finger proteins ZNF512 and ZNF512B specifically localize at pericentric regions through direct DNA binding. Notably, both ZNF512 and ZNF512B are sufficient to initiate de novo heterochromatin formation at ectopically targeted repetitive regions and pericentric regions, as they directly recruit SUV39H1 and SUV39H2 (SUV39H) to catalyse H3K9 methylation. SUV39H2 makes a greater contribution to H3K9 trimethylation, whereas SUV39H1 seems to contribute more to silencing, probably owing to its preferential association with HP1 proteins. ZNF512 and ZNF512B from different species can specifically target pericentric regions of other vertebrates, because the atypical long linker residues between the zinc-fingers of ZNF512 and ZNF512B offer flexibility in recognition of non-consecutively organized three-nucleotide triplets targeted by each zinc-finger. This study addresses two long-standing questions: how constitutive heterochromatin is initiated and how seemingly variable pericentric sequences are targeted by the same set of conserved machinery in vertebrates.

DOI: 10.1038/s41586-024-07640-5

Source: https://www.nature.com/articles/s41586-024-07640-5