Transcription by RNA Polymerase II produces all protein-coding and many non-coding RNA molecules in the cell. The Vlaming group aims to understand how productive transcription over long distances is achieved at protein-coding genes, and conversely, what drives early termination of RNA Polymerase II transcription at many non-coding loci. To this end, we use both advanced high-throughput screening and precise genome editing approaches, and combine this with cutting-edge nascent-RNA sequencing techniques as well as other genome-wide techniques. Deciphering the molecular mechanisms behind this key step in the transcription cycle, will enable studies into misregulation in disease.