Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription.
Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription.
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DOI：
10.1016/j.molcel.2013.07.010
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发表时间：
2013-08-08
期刊：
影响因子：
16
通讯作者：
Glass, Christopher K.
中科院分区：
文献类型：
--
作者：
Kaikkonen, Minna U.;Spann, Nathanael J.;Heinz, Sven;Romanoski, Casey E.;Allison, Karmel A.;Stender, Joshua D.;Chun, Hyun B.;Tough, David F.;Prinjha, Rab K.;Benner, Christopher;Glass, Christopher K.
最近的研究提出了一种分层模型，其中谱系决定因子以协作方式起作用以选择和引发细胞特异性增强子，从而使信号依赖性转录因子以细胞类型特异性方式结合和发挥作用。与该模型一致，TLR 4信号主要通过预先存在的增强子景观调节巨噬细胞基因表达。然而，TLR 4信号传导也诱导约3000个增强子样区域从头启动，使得增强子选择和激活中的中间体可视化。出乎意料的是，我们发现增强子转录先于组蛋白H3赖氨酸4（H3 K4 me 1/2）的局部单甲基化和二甲基化。从头增强子处的H3 K4甲基化主要依赖于组蛋白甲基转移酶Mll 1、Mll 2/4和Mll 3，并且通过抑制RNA聚合酶II延伸而显着降低。总的来说，这些研究结果表明，增强子转录在H3 K4 me 1/2沉积在从头增强子中的重要作用，其独立于所得eRNA转录物的潜在功能。
Recent studies suggest a hierarchical model in which lineage-determining factors act in a collaborative manner to select and prime cell-specific enhancers, thereby enabling signal-dependent transcription factors to bind and function in a cell type-specific manner. Consistent with this model, TLR4 signaling primarily regulates macrophage gene expression through a pre-existing enhancer landscape. However, TLR4 signaling also induces priming of ~3000 enhancer-like regions de novo, enabling visualization of intermediates in enhancer selection and activation. Unexpectedly, we find that enhancer transcription precedes local mono- and di-methylation of histone H3 lysine 4 (H3K4me1/2). H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4 and Mll3, and is significantly reduced by inhibition of RNA polymerase II elongation. Collectively, these findings suggest an essential role of enhancer transcription in H3K4me1/2 deposition at de novo enhancers that is independent of potential functions of the resulting eRNA transcripts.
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影响因子：
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作者：
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Brown, Myles
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