RT Journal Article
SR Electronic
T1 BET inhibition disrupts transcription but retains enhancer-promoter contact
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 848325
DO 10.1101/848325
A1 Nicholas T. Crump
A1 Erica Ballabio
A1 Laura Godfrey
A1 Ross Thorne
A1 Emmanouela Repapi
A1 Jon Kerry
A1 Marta Tapia
A1 Peng Hua
A1 Panagis Filippakopoulos
A1 James O. J. Davies
A1 Thomas A. Milne
YR 2019
UL http://biorxiv.org/content/early/2019/11/20/848325.abstract
AB In higher eukaryotes, enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. The formation of phase condensates is thought to be an essential component of enhancer function. Here, we show that pharmacological targeting of cells with inhibitors of BET (Bromodomain and Extra-Terminal domain) proteins can have a strong impact on transcription but very little impact on enhancer-promoter interactions. Treatment with 1,6-hexanediol, which dissolves phase condensate structures and reduces BET and Mediator protein binding at enhancers, can also have a strong effect on gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further suggest that enhancer-promoter interactions are not dependent on high levels of BRD4 (Bromodomain-containing protein 4) and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and loop extrusion by CTCF/cohesin.