CTCF/cohesin organize the ground state of chromatin-nuclear speckle association

• DOI: 10.1101/2023.07.22.550178
• Publication Date: 2023-07-23T06:40:14Z
• Authors: Ruofan Yu; Shelby Roseman; Allison P. Siegen...; Son C. Nguyen; Eric F. Joyce; Brian B. Liau; Ian D. Krantz; Katherine A. Alex...; Shelley L. Berger
• Keywords: CTCF

Abstract The interchromatin space in the cell nucleus contains various membrane-less nuclear bodies. Recent findings indicate that speckles, comprising a distinct body, exhibit interactions with certain chromatin regions ground state. Key questions are how this state of chromatin-nuclear speckle association is established and what gene regulatory roles layer organization. We report here structural factors CTCF cohesin required for full between DNA speckles. Disruption DNA-speckle contacts via either depletion or had minor effects on basal level expression speckle-associated genes, however we show strong negative stimulus-dependent induction genes. identified putative targeting motif (STM) within subunit RAD21 demonstrated STM association. In contrast to reduction RAD21, releasing factor WAPL stabilized contacts, resulting enhanced inducibility addition, observed disruption patient derived cells Cornelia de Lange syndrome (CdLS), congenital neurodevelopmental diagnosis involving defective pathways, thus revealing speckles as an avenue therapeutic inquiry. summary, our reveal mechanism establish organizational chromatin-speckle association, promote inducibility, relevance human disease.