{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300239/"]},"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=GSE300239"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Chromatin rewiring of β-globin and MYC enhancers by TGF-β1 drives defective erythropoiesis","description":"Erythropoiesis is a tightly regulated process involving rapid cell proliferation with orderly differentiation to ensure production of millions of RBCs. TGF-β1 is a key regulator of erythropoiesis, however, the mechanisms via which it regulates erythropoiesis are not well elucidated. Using myelodysplastic syndromes patient samples, we show that elevated TGF-β1 and SMAD2 signaling correlates with the degree of anemia. Functional studies in primary human HSPCs demonstrate that TGF-β1 exerts a bifurcated effect — suppressing proliferation and inducing premature erythroid differentiation — both of which are rescued by clinical-stage TGFBR1 inhibitor. Through integrative RNA-seq, ChIP-seq, and Micro-C analyses, we found TGF-β1 activates the β-globin LCR, driving early differentiation, while concurrently disrupting the MYC enhancer–promoter interaction to block proliferation. We validated our erythropoiesis defect in vivo by performing single-cell RNA-seq in a TGF-β1 transgenic mouse. Our findings show that TGF-β1/SMAD2 signaling re-wire chromatin to regulate erythropoiesis by affecting β-LCR and MYC super enhancer regions.","dates":{"publication":"2026/07/22"},"accession":"GSE300239","cross_references":{"GSM":["GSM9056179","GSM9056180","GSM9056181","GSM9056182"],"GPL":["18573"],"GSE":["300239"],"taxon":["Homo sapiens"],"PMID":["[42129196]"]}}