DNA methylation patterns of ?-globin cluster in ?-thalassemia patients.

ABSTRACT: Background: Reactivation of fetal hemoglobin (HbF, ?₂?₂) holds a therapeutic target for ?-thalassemia and sickle cell disease. Although many HbF regulators have been identified, the methylation patterns in ?-globin cluster driving the fetal-to-adult hemoglobin switch remains to be determined.

Results: Here, we evaluated DNA methylation patterns of the ?-globin cluster from peripheral bloods of 105 ?⁰/?⁰ thalassemia patients and 44 normal controls. We also recruited 15 bone marrows and 4 cord blood samples for further evaluation. We identified that the CpG sites in the locus control region (LCR) DNase I hypersensitive site 4 and 3 (HS4-3) regions, and ?- and ?-globin promoters displayed hypomethylation in ?⁰/?⁰-thalassemia patients, especially for the patients with high HbF level, as compared with normal controls. Furthermore, hypomethylations in most of CpG sites of the HS4-3 core regions were also observed in bone marrows (BM) of ?⁰/?⁰-patients compared with normal controls; and methylation level of ?-globin promoter -50 and +?17 CpG sites showed lower methylation level in patients with high HbF level compared with those with low HbF level and a negative correlation with HbF level among ?⁰-thalassemia patients. Finally, ?-globin promoter +?17 and +?50 CpG sites also displayed significant hypomethylation in cord blood (CB) tissues compared with BM tissues from normal controls.

Conclusions: Our findings revealed methylation patterns in ?-globin cluster associated with ?⁰ thalassemia disease and ?-globin expression, contributed to understand the epigenetic modification in ?⁰ thalassemia patients and provided candidate targets for the therapies of ?-hemoglobinopathies.

SUBMITTER: Bao X 

PROVIDER: S-EPMC7712619 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature