{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324092/"]},"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=GSE324092"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2 (CordBlood_RNA-seq)","description":"MECOM is a transcription factor critical for the maintenance of hematopoietic stem cells (HSCs) and the pathogenesis of myeloid leukemia. Germline mutations clustered in the C-terminal zinc finger domain (ZFD) of MECOM are known to cause MECOM-associated syndromes, involving bone marrow failure and skeletal anomalies. However, the molecular consequences of these mutations and the precise downstream mechanisms of MECOM remain elusive. Here, we demonstrate that the C-terminal ZFD serves as the dominant DNA-binding module of MECOM, and that disease-associated mutations abrogate its DNA-binding capacity. Mechanistically, we reveal that MECOM functionally antagonizes GATA2 via C-terminal ZFD-mediated DNA binding and recruitment of the corepressor CtBP. This repression promotes myeloid leukemogenesis while suppressing mast cell differentiation. Furthermore, we generated a knockin mouse model harboring a C-terminal ZFD mutation, which successfully recapitulated the clinical phenotypes of MECOM-associated syndromes, including reduction of HSCs and B cells. Collectively, our findings define C-terminal ZFD mutations as loss-of-function mutations with impaired DNA binding, uncover the MECOM-GATA2 axis as a key regulatory pathway, and provide a valuable mouse model for understanding MECOM-associated syndromes.","dates":{"publication":"2026/03/25"},"accession":"GSE324092","cross_references":{"GSM":["GSM9568110","GSM9568111","GSM9568112","GSM9568113","GSM9568114","GSM9568104","GSM9568115","GSM9568105","GSM9568106","GSM9568107","GSM9568108","GSM9568109"],"GPL":["24676"],"GSE":["324092"],"taxon":["Homo sapiens"]}}