Shirai Atsuko, Kawaguchi Takayuki, Shimojo Hideaki, Muramatsu Daisuke, Ishida-Yonetani Mayumi, Nishimura Yoshifumi, Kimura Hiroshi, Nakayama Jun-Ichi, Shinkai Yoichi
Cellular Memory Laboratory, RIKEN, Wako, Japan.
Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki, Japan.
Elife. 2017 Aug 1;6:e25317. doi: 10.7554/eLife.25317.
SUV39H is the major histone H3 lysine 9 (H3K9)-specific methyltransferase that targets pericentric regions and is crucial for assembling silent heterochromatin. SUV39H recognizes trimethylated H3K9 (H3K9me3) via its chromodomain (CD), and enriched H3K9me3 allows SUV39H to target specific chromosomal regions. However, the detailed targeting mechanisms, especially for naïve chromatin without preexisting H3K9me3, are poorly understood. Here we show that Suv39h1's CD (Suv39h1-CD) binds nucleic acids, and this binding is important for its function in heterochromatin assembly. Suv39h1-CD had higher binding affinity for RNA than DNA, and its ability to bind nucleic acids was independent of its H3K9me3 recognition. Suv39h1 bound major satellite RNAs , and knockdown of major satellite RNAs lowered Suv39h1 retention on pericentromere. Suv39h1 mutational studies indicated that both the nucleic acid-binding and H3K9me-binding activities of Suv39h1-CD were crucial for its pericentric heterochromatin assembly. These results suggest that chromatin-bound RNAs contribute to creating SUV39H's target specificity.
SUV39H是主要的组蛋白H3赖氨酸9（H3K9）特异性甲基转移酶，其作用于着丝粒周围区域，对组装沉默异染色质至关重要。SUV39H通过其色域（CD）识别三甲基化的H3K9（H3K9me3），而富集的H3K9me3使SUV39H能够靶向特定的染色体区域。然而，其详细的靶向机制，尤其是对于没有预先存在的H3K9me3的原始染色质的靶向机制，目前了解甚少。在这里，我们表明Suv39h1的CD（Suv39h1-CD）与核酸结合，并且这种结合对其在异染色质组装中的功能很重要。Suv39h1-CD对RNA的结合亲和力高于DNA，并且其结合核酸的能力与其对H3K9me3的识别无关。Suv39h1与主要卫星RNA结合，敲低主要卫星RNA会降低Suv39h1在着丝粒上的保留。Suv39h1突变研究表明，Suv39h1-CD的核酸结合和H3K9me结合活性对其着丝粒周围异染色质组装都至关重要。这些结果表明，与染色质结合的RNA有助于形成SUV39H的靶向特异性。
