Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture.
Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture.
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DOI：
10.1093/nar/gkw1114
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发表时间：
2017-02-28
影响因子：
14.9
通讯作者：
Corces VG
中科院分区：
文献类型：
--
作者：
Cubeñas-Potts C;Rowley MJ;Lyu X;Li G;Lei EP;Corces VG
真核生物基因表达受增强子-启动子相互作用的调控，但调控特异性的分子机制仍然难以捉摸。利用STARR-seq的全基因组研究发现，果蝇中有两类增强子与不同的核心启动子相互作用：内务增强子（hkCP）和发育增强子（dCP）。我们假设这两类增强子被不同的结构蛋白占据，从而影响它们的增强子-启动子接触。通过评估ChIP-seq对结构蛋白、典型增强子相关蛋白和组蛋白修饰的占用，我们确定这两类增强子都富含RNA聚合酶II、CBP和结构蛋白，但也有区别。hkCP增强子含有H3K4me3，只结合Cap-H2、chrochroor、DREF和Z4，而dCP增强子含有H3K4me1，更富集Rad21和Fs(1)h-L。此外，我们利用分辨率< 1kb的Hi-C数据集映射了每个增强子类的相互作用。结果表明，hkCP增强子更有可能形成多个tss相互作用网络，并与拓扑相关结构域（TAD）边界相关，而dCP增强子更多地与一个或两个tss结合，并在染色质环锚点上富集。这些数据支持一个模型，表明增强子内独特的结构蛋白占用是增强子-启动子相互作用特异性的一个贡献者。
Eukaryotic gene expression is regulated by enhancer–promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer–promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions. hkCP enhancers contain H3K4me3 and exclusively bind Cap-H2, Chromator, DREF and Z4, whereas dCP enhancers contain H3K4me1 and are more enriched for Rad21 and Fs(1)h-L. Additionally, we map the interactions of each enhancer class utilizing a Hi-C dataset with <1 kb resolution. Results suggest that hkCP enhancers are more likely to form multi-TSS interaction networks and be associated with topologically associating domain (TAD) borders, while dCP enhancers are more often bound to one or two TSSs and are enriched at chromatin loop anchors. The data support a model suggesting that the unique architectural protein occupancy within enhancers is one contributor to enhancer–promoter interaction specificity.