PDF(Pubmed)
Abstract：
Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.
摘要：
信号诱导的转录程序通过即时早期基因（IEGs）的精确时空激活来调节关键的生物学过程；然而，转录诱导的机制仍然知之甚少。通过将急性耗竭系统与几种基因组学方法相结合来同步询问，时间转录，我们发现KAP1/TRIM28是满足IEGs时间和高度转录需求的第一反应者。在早期刺激时间点，急性KAP1丢失引发RNA聚合酶II延伸动力学增加。这种伸长缺陷在晚期刺激时间点期间通过转录周期使正常进展脱轨。最终导致用于重新启动的转录装置的募集减少，从而抑制了IEGs的转录输出。总的来说，KAP1通过负向调节转录延伸以支持对细胞生理学和生物体功能至关重要的基因的多个转录周期的完全激活而发挥违反直觉的作用。
