Project description:Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear. In this study, we show that a specific enhancer regulator, RACK7, swiftly re-distributes from repressed enhancers to activated enhancers in response to a plethora of acute stimulations. We further show that this process depends on transcription and RACK7 positively regulates enhancer activation by promoting the recruitment of RNA polymerase II. Taken together, our findings suggest that RACK7 senses enhancer activity changes and facilitates their activation during acute stimulations.
Project description:Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear. In this study, we show that a specific enhancer regulator, RACK7, swiftly re-distributes from repressed enhancers to activated enhancers in response to a plethora of acute stimulations. We further show that this process depends on transcription and RACK7 positively regulates enhancer activation by promoting the recruitment of RNA polymerase II. Taken together, our findings suggest that RACK7 senses enhancer activity changes and facilitates their activation during acute stimulations.
Project description:Enhancers regulate dynamic gene expression in a spatiotemporal specific manner. A number of positive as well as negative regulators of enhancers have been reported so far. However, whether and how these regulators sense enhancer activity dynamics remains unclear. In this study, we show that a specific enhancer regulator, RACK7, swiftly re-distributes from repressed enhancers to activated enhancers in response to a plethora of acute stimulations. We further show that this process depends on transcription and RACK7 positively regulates enhancer activation by promoting the recruitment of RNA polymerase II. Taken together, our findings suggest that RACK7 senses enhancer activity changes and facilitates their activation during acute stimulations.
Project description:We identified that RACK7 recognizes the histone H3.3G34R mutaion in vitro. In order to determine the interaction between RACK7 and H3.3G34R mutaion in cells, we used three pediatric glioblastoma (pGBM) cell lines. SJ-HGGx6c(R6) and SJ-HGGx42c(R42) have heterozygous G34R mutation, while SJ-HGGx39c(WT39) has wildtype H3F3A, which encodes H3.3, and we also corrected H3.3G34R in R6 and R42 cells to wildtype H3.3 by CRISPR/Cas9 mediated knock-in. Finally, we performed RACK7 ChIP-seq in these cell lines to explore the function of RACK7 and H3.3G34R mutation.