近日，奥地利分子病理研究所Rushad Pavri课题组发现，Spt5介导的增强子转录直接偶联增强子激活与启动子相互作用。相关论文于2020年4月6日在线发表在《自然—遗传学》杂志上。

Title: Spt5-mediated enhancer transcription directly couples enhancer activation with physical promoter interaction

Author: Johanna Fitz, Tobias Neumann, Monika Steininger, Eva-Maria Wiedemann, Adriana Cantoran Garcia, Alexander Athanasiadis, Ursula E. Schoeberl, Rushad Pavri

Issue&Volume: 2020-04-06

Abstract: Active enhancers are frequently transcribed, yet the regulatory role of enhancer transcription remains debated. Here, we depleted the RNA polymerase II pausing and elongation factor Spt5 in activated mouse B cells and found that approximately 50% of enhancer–gene pairs showed co-regulated transcription, consistent with a potential functional requirement for enhancer transcription. In particular, Spt5 depletion led to loss of super-enhancer–promoter physical interaction and gene expression at the immunoglobulin heavy-chain locus (Igh), abrogating antibody class switch recombination. This defect correlated strictly with loss of enhancer transcription but did not affect acetylation of histone H3 at lysine 27, chromatin accessibility and occupancy of Mediator and cohesin at the enhancer. Strikingly, CRISPRa-mediated rescue of enhancer transcription in Spt5-depleted cells restored Igh gene expression. Our work suggests that Spt5-mediated enhancer transcription underlies the physical and functional interaction between a subset of active enhancers and their target promoters.

DOI: 10.1038/s41588-020-0605-6

Source: https://www.nature.com/articles/s41588-020-0605-6