Project description:What controls enhancer-promoter communication to allow for cis-transcriptional regulation remains a mystery. Here we studied how transcriptional dynamics shapes enhancer-promoter contacts. We demonstrate that enhancer function is reflected in enhancer-promoter contacts frequency which highly depend on active transcription. Pol II pausing, which is widespread across metazoan enhancers and promoters, has a direct effect on focal enhancer-promoter contacts. We confirmed this effect by depleting NELFB, a subunit of the negative elongation factor complex and a pivotal factor in Pol II pausing. Moreover, the catalytic activity of PARP1, a regulator of transcription and chromatin condensation, stabilizes enhancer-promoter contacts globally, but can destabilize contacts by promoting Pol II escape from pausing. Based on these findings, we propose an updated model that couples transcription and enhancer-promoter contacts.
Project description:What controls enhancer-promoter communication to allow for cis-transcriptional regulation remains a mystery. Here we studied how transcriptional dynamics shapes enhancer-promoter contacts. We demonstrate that enhancer function is reflected in enhancer-promoter contacts frequency which highly depend on active transcription. Pol II pausing, which is widespread across metazoan enhancers and promoters, has a direct effect on focal enhancer-promoter contacts. We confirmed this effect by depleting NELFB, a subunit of the negative elongation factor complex and a pivotal factor in Pol II pausing. Moreover, the catalytic activity of PARP1, a regulator of transcription and chromatin condensation, stabilizes enhancer-promoter contacts globally, but can destabilize contacts by promoting Pol II escape from pausing. Based on these findings, we propose an updated model that couples transcription and enhancer-promoter contacts.
Project description:What controls enhancer-promoter communication to allow for cis-transcriptional regulation remains a mystery. Here we studied how transcriptional dynamics shapes enhancer-promoter contacts. We demonstrate that enhancer function is reflected in enhancer-promoter contacts frequency which highly depend on active transcription. Pol II pausing, which is widespread across metazoan enhancers and promoters, has a direct effect on focal enhancer-promoter contacts. We confirmed this effect by depleting NELFB, a subunit of the negative elongation factor complex and a pivotal factor in Pol II pausing. Moreover, the catalytic activity of PARP1, a regulator of transcription and chromatin condensation, stabilizes enhancer-promoter contacts globally, but can destabilize contacts by promoting Pol II escape from pausing. Based on these findings, we propose an updated model that couples transcription and enhancer-promoter contacts.
Project description:Here, we examined the interactions between PRMT6, poly(ADP-ribose) polymerase 1 (PARP1), and the cullin 4 B (CUL4B)-Ring E3 ligase (CRL4B) complex, to form a transcription-repressive complex that co-occupies the core clock gene PER3 promoter.