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 (1,2). 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.

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

Mara Maldotti
First
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Andrea Lauria;Francesca Anselmi;Ivan Molineris;Annalaura Tamburrini;Guohua Meng;Isabelle Laurence Polignano;Mirko Giuseppe Scrivano;Stefania Rapelli;Edoardo Morandi;Salvatore Oliviero
Last
2022

Abstract

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 (1,2). 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.
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https://pubmed.ncbi.nlm.nih.gov/35137201/
Chromatin, Epigenetics, acetylation, p300, lncRNAs.
Mara Maldotti , Andrea Lauria, Francesca Anselmi , Ivan Molineris, Annalaura Tamburrini, Guohua Meng, Isabelle Laurence Polignano , Mirko Giuseppe Scrivano, Fabiola Campestre, Lisa Marie Simon, Stefania Rapelli, Edoardo Morandi, Danny Incarnato, Salvatore Oliviero
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1846534
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