Chromatin-bound RB targets promoters, enhancers, and CTCF-bound loci and is redistributed by cell-cycle progression.
Chromatin-bound RB targets promoters, enhancers, and CTCF-bound loci and is redistributed by cell-cycle progression.
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DOI：
10.1016/j.molcel.2022.07.014
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发表时间：
2022-09-15
期刊：
影响因子：
16
通讯作者：
Lawrence, Michael S.
中科院分区：
文献类型：
--
作者：
Sanidas, Ioannis;Lee, Hanjun;Rumde, Purva H.;Boulay, Gaylor;Morris, Robert;Golczer, Gabriel;Boulay, Hanjun Gaylor;Stanzione, Marcelo;Hajizadeh, Soroush;Zhong, Jun;Ryan, Meagan B.;Corcoran, Ryan B.;Drapkin, Benjamin J.;Rivera, Miguel N.;Dyson, Nicholas J.;Lawrence, Michael S.
RB与染色质的相互作用是理解其分子功能的关键。在这里，我们第一次确定了染色质结合RB的全光谱。RB并非如通常描述的那样专门结合启动子，而是靶向三种基本上不同类型的基因座（启动子、增强子、绝缘子），这三种基因座在很大程度上可通过E2 F1、c-Jun和CTCF的互斥存在来区分。虽然E2 F/DP促进RB与启动子的结合，但AP-1将RB募集到增强子。虽然在CDK位点的磷酸化往往描绘释放RB从染色质，我们表明，细胞周期重新分配RB，使其丰富的启动子在G1期，并在非启动子位点的循环细胞。RB结合的启动子包括经典的E2 F靶点，并且在谱系之间是相似的，但是RB结合的增强子与不同类别的基因相关，并且在细胞类型之间变化。因此，RB在G1中控制E2 F的作用得到了很好的保护，并且当细胞进入S期时，它靶向细胞类型特异性增强子和CTCF位点。Sanidas等人表明，RB不是专门靶向E2 F启动子，而是与特定组的启动子、增强子和绝缘子结合以靶向不同的基因组。细胞周期进程将RB重新分配给细胞类型特异性增强子。PanChIP软件证实RB与不同类型基因座的不同转录因子相关。
RB’s interaction with chromatin is key to understanding its molecular functions. Here, for first time, we identify the full spectrum of chromatin-bound RB. Rather than exclusively binding promoters, as is often described, RB targets three fundamentally different types of loci (promoters, enhancers, insulators), which are largely distinguishable by the mutually exclusive presence of E2F1, c-Jun, and CTCF. While E2F/DP facilitates RB association with promoters, AP-1 recruits RB to enhancers. Although phosphorylation in CDK-sites is often portrayed to release RB from chromatin, we show that the cell-cycle redistributes RB so that it enriches at promoters in G1, and at non-promoter sites in cycling cells. RB-bound promoters include the classic E2F-targets and are similar between lineages, but RB-bound enhancers associate with different categories of genes and vary between cell types. Thus, RB has a well-preserved role controlling E2F in G1, and it targets cell type-specific enhancers and CTCF-sites when cells enter S-phase. Sanidas et al. show that, rather than exclusively targeting E2F-promoters, RB associates with specific groups of promoters, enhancers, and insulators to target different sets of genes. Cell cycle progression redistributes RB towards cell type-specific enhancers. PanChIP software confirms that RB associates with distinct transcription factors at different types of loci.
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