State-of-Art Genomics to Reveal Mechanisms of Transcription at Genes and Enhancers in Health and Disease

Dynamic regulation of RNA polymerase at promoters and enhancers defines transcriptional programs and coordinates the establishment of cell types and cellular responses in heath and disease.

Transcription has been extensively investigated at individual genes, but the mechanisms that coordinate RNA polymerase molecules across the genome remain unknown, particularly in development, signal responses and disease states.

In recently established Molecular Genomics laboratory (KTH and SciLifeLab, Stockholm), we interrogate in molecular detail how transcription and chromatin dynamics are coordinated at genes and enhancer in cultured cells, tissue samples and patient material.

In the heart of our studies are high-resolution techniques that track engaged RNA Polymerase complexes at nucleotide resolution across the genome, and measure chromatin architecture and dynamics.

In particular, we use and develop methods that follow Pol II complexes and their molecular interactions, providing accurate spatiotemporal measures of initiation, pausing, elongation, termination and co-transcriptional RNA processing genome-wide.

We have recently revealed how genome architecture primes transcriptional responses, how promoter-proximal pause-release coordinates rapid transcriptional reprogramming, and how cells establish and retain a trascriptional memory.

Here, the advanced techniques are brought to physiologically relevant contexts to map reprogramming of transcription in development and disease.