Promoter regulation codes in early embryos and cancer
In this study we asked, how do the very first genes escape the globally repressive chromatin environment to get activated during zygotic genome activation. We describe the dissection of the genetic mechanisms involved in the formation of a large nuclear transcription body, which provides a unique environment for the first genes to get activated in the zebrafish embryo. We used Nanopore long read genome sequencing, genome editing and in vivo imaging of nascent transcription and its genomic loci, to demonstrate how the transcription body is formed by uniquely extreme promoter density of miR-430 genes. We show how the gene promoter cluster, which seeds the transcription body also act as an ‘organiser’ for distal, mostly zinc finger protein genes occupying the same chromosomal territory. Thus, the hundreds of promoters function as the first enhancers before topology associated domains emerge. Zinc finger genes, which are selectively activated in the transcription body share core promoter architecture features with that of the transcription body organiser genes, but are distinguished from paralogues genes residing in the same chromosomal territory, which remain unaffected. Our observations suggest a role for core promoter specificity in enhancing distal gene activation in the transcription body, which forms during genome activation.
- Ferenc Mueller
- Institute of Cancer and Genomic Sciences, University of Birmingham Royaume-Uni