SET1 复合物通过与 CpG 岛染色质的多价相互作用选择活跃转录的靶基因。

The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.

机构信息

Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.

Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

出版信息

Cell Rep. 2017 Sep 5;20(10):2313-2327. doi: 10.1016/j.celrep.2017.08.030.

Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3). CFP1 defines SET1 complex occupancy on chromatin, and its multivalent interactions are required for the SET1 complex to place H3K4me3. In the absence of CFP1, gene expression is perturbed, suggesting that normal targeting and function of the SET1 complex are central to creating an appropriately functioning vertebrate promoter-associated epigenome.

染色质修饰和与启动子相关的表观基因组对于基因表达的调控非常重要。然而，染色质修饰复合物在脊椎动物中被靶向到适当的基因启动子的机制以及它们如何影响基因表达仍然知之甚少。在这里，我们使用活细胞成像和功能基因组学的组合，发现脊椎动物 SET1 复合物通过 CFP1 被靶向到活跃转录的基因启动子，CFP1 参与了一种多价染色质读取，涉及识别非甲基化的 DNA 和组蛋白 H3 赖氨酸 4 三甲基化 (H3K4me3)。CFP1 定义了 SET1 复合物在染色质上的占据，其多价相互作用对于 SET1 复合物放置 H3K4me3 是必需的。在没有 CFP1 的情况下，基因表达受到干扰，这表明 SET1 复合物的正常靶向和功能对于创建一个功能正常的脊椎动物启动子相关表观基因组至关重要。