Transcription factor trapping by RNA in gene regulatory elements (GRO-Seq)

Transcription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. GRO-Seq in mouse embryonic stem cells treated with transcription-altering drugs

转录因子（Transcription factors, TFs）通过结合启动子近端与远端DNA元件中的特定序列，调控基因转录。RNA可从启动子近端及远端DNA元件中转录获得，且已有研究证实部分结合DNA的转录因子亦可结合RNA。基于上述观察结果，我们提出假说：来自调控元件的转录RNA可帮助稳定转录因子在这些调控元件上的占据情况。本研究证实，广泛表达的转录因子YY1可结合近端与远端调控元件，以及胚胎干细胞（embryonic stem cells）中活性基因附近与这些元件相关的RNA分子。抑制这些元件的转录会降低YY1的占据水平。反之，将RNA分子锚定在YY1的DNA结合位点附近，则可提升YY1的占据水平。我们据此提出，RNA可作为捕获因子，将特定转录因子维持在活性增强子与启动子近端的调控元件上。因此，转录调控通常存在一个正反馈环路：YY1与其他转录因子可刺激局部转录，而新合成的新生RNA则会进一步强化局部的转录因子占据情况。该模型有助于解释为何在哺乳动物基因组中，转录因子仅会在可检测到转录的区域结合其共有基序的极小一部分。经转录改变药物处理的小鼠胚胎干细胞的GRO-Seq数据集