{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328958/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328958"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A conformation-sensitive product inhibitor of HDAC1/2 potentiates WNT/β-catenin signaling [ChIP-seq]","description":"Pharmacological enhancement of WNT/β-catenin signaling holds promises for tissue repair and regeneration. Here, we identify WNA1, an isoxazole-based small molecule, as a potent activator of WNT/β-catenin signaling. WNA1 stimulates β-catenin signaling in different cellular contexts, and this activity requires production of endogenous WNT. In vivo, WNA1 promotes skin hair growth, consistent with the established role of β-catenin signaling in hair follicle development. Intriguingly, WNA1 increases histone acetylation with minimal activity on uncomplexed recombinant histone deacetylases (HDACs), while conventional HDAC inhibitors exhibit minimal β-catenin-stabilizing activity. We demonstrate that β-catenin signaling is repressed by the HDAC1/2-containing NuRD complex, and that WNA1 enhances β-catenin signaling through selectively inhibiting HDAC1/2. Structural and biochemical analyses reveal that WNA1 is hydrolyzed by the HDAC1-MTA1 complex, and its product is trapped in the foot-pocket of HDAC1 in an InsP6-dependent manner. HDAC1 mutants with reduced foot-pocket abrogate WNA1-induced histone acetylation and β-catenin accumulation. These findings establish WNA1 as a conformation-sensitive, foot-pocket-anchored product inhibitor that selectively targets complex-bound HDAC1/2. Our study reveals a unique mechanism for HDAC1/2 inhibition and WNT potentiation, paving the way for therapeutic applications.","dates":{"publication":"2026/09/01"},"accession":"GSE328958","cross_references":{"GSM":["GSM9694879","GSM9694878","GSM9694886","GSM9694885","GSM9694888","GSM9694887","GSM9694882","GSM9694881","GSM9694884","GSM9694883","GSM9694880","GSM9694889","GSM9694869","GSM9694875","GSM9694874","GSM9694896","GSM9694877","GSM9694876","GSM9694871","GSM9694893","GSM9694892","GSM9694870","GSM9694895","GSM9694873","GSM9694894","GSM9694872","GSM9694891","GSM9694890"],"GPL":["16791"],"GSE":["328958"],"taxon":["Homo sapiens"]}}