Biology

Dr. Venkata Chalamcharla
National Cancer Institute/National Institutes of Health, Bethesda, USA

Epigenetically heritable domains of heterochromatin prevent the inopportune expression of developmental genes, and suppress non-coding RNAs derived from repetitive DNA elements and retrotransposons, which pose a particular threat to genome stability. Paradoxically, heterochromatin assembly is dependent on transcription of these loci. Figuring out how transcriptional activity promotes gene silencing at specific regions of the genome has remained a central challenge in the chromatin field. Using the fission yeast Schizosaccharomyces pombe as a model system, I discovered that heterochromatic transcripts are subject to premature 3’-end formation by specialized RNA surveillance/quality-control factors. These factors are also required to assemble heterochromatin, suggesting that abnormal RNA 3’-end processing triggers heterochromatin formation. Remarkably, I found that the conserved RNA polymerase II termination factor Dhp1^Xrn2/Rat1 is integral to the assembly of all RNA-based facultative and constitutive heterochromatin domains, providing a unifying theme for RNA-based heterochromatin formation.