Institut André Lwoff, Centre National de la Recherche Scientifique, FRE2944, Université Paris-Sud, 94800 Villejuif, France.
Mol Cell. 2010 Jan 15;37(1):46-56. doi: 10.1016/j.molcel.2009.12.017.
Lysine 9 of histone 3 (H3K9) can be mono-, di-, or trimethylated, inducing distinct effects on gene expression and chromatin compaction. H3K9 methylation can be mediated by several histone methyltransferases (HKMTs) that possess mono-, di-, or trimethylation activities. Here we provide evidence that a subset of each of the main H3K9 HKMTs, G9a/KMT1C, GLP/KMT1D, SETDB1/KMT1E, and Suv39h1/KMT1A, coexist in the same megacomplex. Moreover, in Suv39h or G9a null cells, the remaining HKMTs are destabilized at the protein level, indicating that the integrity of these HKMTs is interdependent. The four HKMTs are recruited to major satellite repeats, a known Suv39h1 genomic target, but also to multiple G9a target genes. Moreover, we report a functional cooperation between the four H3K9 HKMTs in the regulation of known G9a target genes. Altogether, our data identify a H3K9 methylation multimeric complex.
组蛋白 3 的赖氨酸 9（H3K9）可以单、二或三甲基化，从而对基因表达和染色质紧缩产生不同的影响。H3K9 甲基化可以由几种具有单、二或三甲基化活性的组蛋白甲基转移酶（HKMTs）介导。在这里，我们提供的证据表明，每种主要的 H3K9 HKMT（G9a/KMT1C、GLP/KMT1D、SETDB1/KMT1E 和 Suv39h1/KMT1A）的子集都存在于同一个大复合物中。此外，在 Suv39h 或 G9a 缺失细胞中，其余的 HKMTs 在蛋白质水平上不稳定，表明这些 HKMTs 的完整性是相互依存的。这四种 HKMTs 被招募到主要卫星重复序列，这是已知的 Suv39h1 基因组靶标，但也被招募到多个 G9a 靶基因。此外，我们报告了四种 H3K9 HKMT 在调节已知 G9a 靶基因中的功能合作。总之，我们的数据确定了一个 H3K9 甲基化多聚体复合物。
