Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, Maryland 20892, USA.
Nat Commun. 2012 Jan 17;3:633. doi: 10.1038/ncomms1652.
Transcription is a multi-stage process that coordinates several steps within the transcription cycle including chromatin reorganization, RNA polymerase II recruitment, initiation, promoter clearance and elongation. Recent advances have identified the super elongation complex, containing the eleven-nineteen lysine-rich leukaemia (ELL) protein, as a key regulator of transcriptional elongation. Here we show that ELL has a diverse and kinetically distinct role before its assembly into the super elongation complex by stabilizing Pol II recruitment/initiation and entry into the pause site. Loss of ELL destabilizes the pre-initiation complexes and results in disruption of early elongation and promoter proximal chromatin structure before recruitment of AFF4 and other super elongation complex components. These changes result in significantly reduced transcriptional activation of rapidly induced genes. Thus, ELL has an early and essential role during rapid high-amplitude gene expression that is required for both Pol II pause site entry and release.
转录是一个多阶段的过程，协调转录周期内的几个步骤，包括染色质重排、RNA 聚合酶 II 的募集、起始、启动子清除和延伸。最近的进展确定了超级延伸复合物，包含十一号十九号赖氨酸丰富的白血病 (ELL) 蛋白，作为转录延伸的关键调节剂。在这里，我们表明 ELL 在组装成超级延伸复合物之前具有多样化和动力学上不同的作用，通过稳定 Pol II 的募集/起始和进入暂停位点。ELL 的缺失会使起始前复合物不稳定，并导致在招募 AFF4 和其他超级延伸复合物成分之前，早期延伸和启动子近端染色质结构的破坏。这些变化导致快速诱导基因的转录激活显著减少。因此，ELL 在快速高振幅基因表达过程中具有早期和必不可少的作用，这是 Pol II 暂停位点进入和释放所必需的。
