PLX172480

GSE139436: BET protein inhibition disrupts transcription without altering enhancer-promoter interactions [RNA-seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

In higher eukaryotes, enhancers are DNA sequences that allow for the 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. Here, we show that treatment of cells with inhibitors of BET 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 potentially separable events. Our findings further suggest that maintenance of enhancer-promoter interactions, although not sufficient for the maintenance of gene transcription, is are not dependent on high levels of BRD4 and Mediator, and are likely controlled maintained by a complex set of factors including low level binding of activator complexes and loop extrusion by CTCF/cohesin. SOURCE: Thomas,A,Milne (thomas.milne@imm.ox.ac.uk) - University of Oxford