The acetyltransferase p300 is recruited in trans to multiple enhancer sites by lncSmad7

The histone acetyltransferase p300 (also known as KAT3B) is a general transcriptional coactivator that introduces the H3K27ac mark on enhancers triggering their activation and gene transcription. Genome-wide screenings demonstrated that a large fraction of long non-coding RNAs (lncRNAs) plays a role in cellular processes and organ development although the underlying molecular mechanisms remain largely unclear (,). We found 122 lncRNAs that interacts directly with p300. In depth analysis of one of these, lncSmad7, is required to maintain ESC self-renewal and it interacts to the C-terminal domain of p300. lncSmad7 also contains predicted RNA-DNA Hoogsteen forming base pairing. Combined Chromatin Isolation by RNA precipitation followed by sequencing (ChIRP-seq) together with CRISPR/Cas9 mutagenesis of the target sites demonstrate that lncSmad7 binds and recruits p300 to enhancers in trans, to trigger enhancer acetylation and transcriptional activation of its target genes. Thus, these results unveil a new mechanism by which p300 is recruited to the genome.

Automated summary

The histone acetyltransferase p300 plays a role in introducing H3K27ac mark on enhancers, triggering their activation and gene transcription. Long non-coding RNAs (lncRNAs) have been found to be involved in cellular processes and organ development, including 122 lncRNAs that directly interact with p300. One of them, lncSmad7, interacts with the C-terminal domain of p300 and is necessary for maintaining ESC self-renewal. By recruiting p300 to enhancers, lncSmad7 activates transcription of its target genes through enhancer acetylation.