Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of ß-hemoglobinopathies [4C]

We have identified putative repressor region (PRR) to exon-1 of ß-globin (ßE1) in the ß-globin cluster as a core region in alll the HPFH deletions that activates fetal hemoglobin and silences adult hemoglobin. To test the impact of PRR-ßE1 gene editing in ß-globin cluster configuration, we employed Circular chromosome conformation capture (4C) analysis to assess the LCR interaction to the gamma-globin promoter. Using HBG2 promoter as viewpoint,4C analysis showed an increased interaction of HBG promoter to the hypersensitive (HS) sites of the LCR in HUDEP-2 clones harbouring PRR-ßE1 biallelic deletions compared to control HUDEP-2 cells. Link for 4C output files Mendeley - Venkatesan, Vigneshwaran (2022), “4C data set ”, Mendeley Data, V1, doi: 10.17632/cz3thnr9kf.1 Overall design: 4-C