{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345461/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345461"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RNA fine-tunes KAT5 activity to shape chromatin acetylation during active transcription [RNA-Seq]","description":"KAT5 is a prominent histone acetyltransferase that deposits acetylation on histone H4 to regulate transcription, genome stability, and cell fate decisions. Although the chromatin recruitment of KAT5 and its associated NuA4/TIP60 complex is well characterized, the molecular mechanisms that regulate its catalytic activity are still largely unknown. Here, we identify RNA as a direct and reversible modulator of KAT5 activity. Using single-end enhanced crosslinking and immunoprecipitation sequencing (seCLIP-seq), we find that KAT5 binds RNA in cells with a strong preference for GC-rich mRNA sequences enriched near transcription start sites. Unexpectedly, loss of KAT5–RNA interactions during acute transcriptional inhibition triggers rapid and pronounced promoter hyperacetylation in a KAT5-dependent manner. Biochemical and structural analyses reveal that RNA engages a regulatory RNA-binding region within the HAT domain, sterically blocking substrate access to the catalytic pocket and thereby suppressing KAT5 acetyltransferase activity. Our findings uncover nascent RNA as a reversible allosteric inhibitor of KAT5, revealing an RNA-directed feedback mechanism that modulates promoter acetylation and transcriptional output.","dates":{"publication":"2026/09/22"},"accession":"GSE345461","cross_references":{"GSM":["GSM10004960","GSM10004958","GSM10004959","GSM10004954","GSM10004955","GSM10004956","GSM10004957","GSM10004961","GSM10004962","GSM10004952","GSM10004963","GSM10004953"],"GPL":["34295"],"GSE":["345461"],"taxon":["Homo sapiens"]}}