Where to start in the DNA transcription process
RNA polymerase II (RNAPII) is an enzyme that catalyses the transcription of DNA to produce precursors for the next step in protein synthesis. The EU-funded DTSSCP (Determinants of mammalian transcription start site selection and core promoter usage) project has looked at transcription initiation from two standpoints – DNA sequence and epigenetic chromatin changes. The researchers found that chromatin accuracy can predict core promoter location, amount of RNAPII at the promoter and the amount of messenger RNA at the promoter. Rate-limiting control of gene activation by RNAPII stalling could also be anticipated from the histone modifications around the TSS. Analysing distribution of small RNAs upstream, within and downstream of TSSs, the project team found that asymmetric sequence distribution around human gene promoters results in a directional RNA output from an otherwise bidirectional transcription process. Promoter sequences can therefore be linked to either abortive transcription or RNAPII elongation. Enhancers upregulate the transcription of TSSs. The scientists produced an enhancer atlas to identify disease-associated single nucleotide changes and to distinguish between ubiquitous and cell specific enhancers. Furthermore, enhancer redundancy explains gene expression strength. The implications of this research are far-reaching as control of gene expression is crucial for balanced and effective development in all organisms. Research results have been published in high-profile journals like Nature, BMC Genomics and Trends in Genetics, and Nature Structural and Molecular Biology.
Keywords
DNA transcription, transcription start site, RNAPII, promoter, enhancer
