Project name: RNA polymerase II and PARP1 shape enhancer-promoter contacts [CUT&Tag]

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.Overall design: CUT&Tag libraries were prepared using antibody against the N-terminal of PARP1 (Active Motif, AB_2793257) or anti-IgG antibody (Cell signaling, Normal Rabbit IgG #2729), with two replicates for each antibody.

Data type: Epigenomics

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2022-06-13