Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.
|Title||Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.|
|Publication Type||Journal Article|
|Year of Publication||2023|
|Authors||Islam Z, Saravanan B, Walavalkar K, Farooq U, Singh AKumar, Sabarinathan R, Thakur J, Pandit A, Henikoff S, Notani D|
|Date Published||2023 Jan 17|
Vertebrate genomes are partitioned into chromatin domains or topologically associating domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at domain boundaries correlates with better insulation; however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant and TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer-promoter interactions, and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters, we show that active TAD enhancers, but not promoters, induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.
|Alternate Journal||Genome Res|