Functional analysis and targeted manipulation of chromatin dynamics on mammalian rRNA genes and Nucleolar Organizer Regions (NORs) (A35*)

点击翻译按钮获取中文摘要

Levels of ribosomal RNAs and, as a consequence, rates of protein translation change during development and differ remarkably across cell types. Despite their importance however, very little is known about how rRNA genes are regulated by chromatin mechanisms. We have recently developed a strategy allowing targeted manipulation of rDNA chromatin in vitro and in vivo using gRNA multiplexing and dCas9 approaches. Now, we will use this strategy to manipulate a number of rDNA chromatin components (UBF, PARP, FACT) and mechanisms (DNA methylation, nucleosome remodelling, noncoding transcription, metabolic signalling), to investigate, which of those are causally determining rRNA expression, cellular protein translation rates and mammalian stem cell behaviour.