RNA binding limits the ligand induced transcriptional potential of estrogen receptor-alpha (ERα)

Abstract

AbstractTranscription factors (TFs) primarily regulate gene expression by binding to DNA through their DNA binding domains (DBD). Additionally, approximately half of these TFs also interact with RNA. However, the role of RNA in enabling TF binding on chromatin and subsequent transcription is poorly understood. Estrogen receptor-α (ERα) is one such TF that activates genes in response to estrogen stimulation. Here, we report that ERα interacts with various types of RNAs in ligand dependent manner via its RNA binding motif in hinge region. RNA binding defects lead to a global loss of ERα binding in the genome, particularly at weaker ERα motifs. In the absence of RNA binding, the ERα exhibits dynamic behavior in the nucleus and unexpectedly, the dynamic binding coincides with robust polymerase loading on ERα bound chromatin regions. The higher occupancy of PolII was recapitulated by robust ligand induced transcription of ERα-regulated genes. Collectively, our results suggest that RNA interactions strengthen ERα binding to chromatin limiting the ligand-dependent transcriptional upregulation of estrogen-induced genes.