Elongin A displays widespread association with actively transcribed genes and modulates enhancer RNA transcripiton.
Elongin A (EloA) is an essential transcription factor that stimulates the rate of RNA polymerase II (Pol II) transcription elongation in vitro. However, its role as a transcription factor in vivo has remained underexplored. Here we show that in mouse embryonic stem cells, EloA localizes both to thousands of Pol II transcribed genes with a preference for sites of Pol II pausing and as well as a large number of active enhancers across the genome. EloA loss results in accumulation of transcripts at a subset of enhancers and their adjacent genes. However, EloA deletion results in only a modest decrease in the average elongation rate of Pol II globally. We also show that EloA localizes to the nucleoli and associates with RNA polymerase I transcribed ribosomal RNA gene, Rn45s. EloA is a highly disordered protein, which we demonstrate forms phase-separated condensates in vitro, and truncation mutations in the intrinsically disordered regions (IDR) of EloA interferes with its targeting and localization to the nucleoli. We conclude that EloA broadly associates with transcribed regions, tunes RNA Pol II transcription levels via impacts on eRNA synthesis and interacts with the rRNA producing/processing machinery in the nucleolus. Overall design: We performed Cut&Run-seq and ChIP-seq  experiments on murine CCE28 embryonic stem cells (wild-type & ELoA null, Kind gift of Dr. Teijiro Aso at Kochi Medical School) to investigate the genome wide distribution of EloA .  We also investigated the effect of EloA loss on  transcription and transcription elongation rate by performing Bru-seq to detect nascent transcription in wild-type and EloA null mESC.