Project description:This experiment aimed at understanding the correlation between RNA polymerase II occupancy and cell size. For this, we used three strains of increasing average size (wee1-50 < wt < cdc25-22) and performed ChIP-seq experiments using anti-CTD antibodies.
Project description:Organisms regulate cell size and shape to function efficiently. Aberrant cell morphogenesis is commonly associated with disease, yet gene-regulatory mechanisms remain unknown. CISTR-ACT was the first lncRNA involved in inter-chromosomal contacts and Mendelian disease, and is associated with mean corpuscular volume (red blood cell size). Here, functional dissection of CISTR-ACT’s DNA- and RNA-encoded mechanisms by in vitro and in vivo perturbations reveal that CISTR-ACT regulates cell size across cell types and species. CISTR-ACT’s locus is embedded in a stable inter-chromosomal environment which contains cell size genes that are regulated by CISTR-ACT in trans. CISTR-ACT’s RNA also has function and directly interacts with transcription factor FOSL2 to guide its regulation of cell morphogenesis and cell-cell adhesion genes. In the absence of CISTR-ACT, the FOSL2-chromatin binding is perturbed. Our study exemplifies how a functionally conserved lncRNA regulates cell size with multiple modes of action and ultimately contributes to clinically relevant phenotypes.