异常增强子激活是许多癌症中促进癌基因表达的关键机制。虽然对真核生物中更大染色体区域调控的机制已有较多了解，但对增强子-启动子相互作用的细节仍知之甚少。最近的研究表明，像BRD4和Mediator这样的共同激活因子对增强子-启动子相互作用几乎没有影响。在由MLL-AF4融合蛋白控制的白血病中，我们使用超高分辨率技术Micro-Capture-C（MCC）展示了MLL-AF4结合促进增强子-启动子相互作用的广泛、高密度区域存在于一部分关键靶点中。这些增强子富集于PAF1C和FACT等转录延伸因子，并且失去这些因子会废除增强子-启动子接触。这项研究不仅为MLL-AF4如何在白血病中驱动关键基因的高水平转录提供了另一个模型，还暗示了一个更一般的模型，将增强子-启动子相互作用和转录延伸联系起来。© 2023. Springer Nature Limited.

Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.© 2023. Springer Nature Limited.