{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318569/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318569"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RNA fine-tunes KAT5 activity to shape chromatin acetylation during active transcription [seCLIP-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":"GSE318569","cross_references":{"GSM":["GSM9497729","GSM10015309","GSM9497726","GSM9497725","GSM9497728","GSM9497727","GSM10015304","GSM9497724","GSM10015308","GSM10015307","GSM10015306","GSM10015305"],"GPL":["34295"],"GSE":["318569"],"taxon":["Homo sapiens"]}}