{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Peslak SA"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pagination":["452-465"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9958407"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31"],"pubmed_abstract":["Transcriptional enhancers can be in physical proximity of their target genes via chromatin looping. The enhancer at the β-globin locus (locus control region [LCR]) contacts the fetal-type (<i>HBG</i>) and adult-type (<i>HBB</i>) β-globin genes during corresponding developmental stages. We have demonstrated previously that forcing proximity between the LCR and <i>HBG</i> genes in cultured adult-stage erythroid cells can activate <i>HBG</i> transcription. Activation of <i>HBG</i> expression in erythroid cells is of benefit to patients with sickle cell disease. Here, using the β-globin locus as a model, we provide proof of concept at the organismal level that forced enhancer rewiring might present a strategy to alter gene expression for therapeutic purposes. Hematopoietic stem and progenitor "],"journal":["Molecular therapy. Nucleic acids"],"pubmed_title":["Forced enhancer-promoter rewiring to alter gene expression in animal models."],"pmcid":["PMC9958407"],"funding_grant_id":["R01 HL119479","T32 DK007780","R01 DK127738","R01 CA271523","R01 HL095675","K08 DK129716"],"pubmed_authors":["Leonard A","Jiang J","Wielgosz M","Bhardwaj SK","Abdulmalik O","Demirci S","Hinds M","Bonifacino AC","Tisdale JF","Weiss MJ","Throm RE","Chandra V","Le A","Linde NS","Ferrara F","Uchida N","Chu R","Germino-Watnick P","Blobel GA","Rupon JW","Ryu B","Tong W","Hamagami N","Peslak SA","Essawi K","Krouse AE","Donahue RE"],"additional_accession":[]},"is_claimable":false,"name":"Forced enhancer-promoter rewiring to alter gene expression in animal models.","description":"Transcriptional enhancers can be in physical proximity of their target genes via chromatin looping. The enhancer at the β-globin locus (locus control region [LCR]) contacts the fetal-type (<i>HBG</i>) and adult-type (<i>HBB</i>) β-globin genes during corresponding developmental stages. We have demonstrated previously that forcing proximity between the LCR and <i>HBG</i> genes in cultured adult-stage erythroid cells can activate <i>HBG</i> transcription. Activation of <i>HBG</i> expression in erythroid cells is of benefit to patients with sickle cell disease. Here, using the β-globin locus as a model, we provide proof of concept at the organismal level that forced enhancer rewiring might present a strategy to alter gene expression for therapeutic purposes. Hematopoietic stem and progenitor ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2025-05-18T12:54:12.213Z","creation":"2025-05-18T12:54:12.213Z"},"accession":"S-EPMC9958407","cross_references":{"pubmed":["36852088"],"doi":["10.1016/j.omtn.2023.01.016"]}}