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DNA methylation patterns of β-globin cluster in β-thalassemia patients

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

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Autores principales: Bao, Xiuqin, Zuo, Yangjin, Chen, Diyu, Zhao, Cunyou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712619/
https://www.ncbi.nlm.nih.gov/pubmed/33272312
http://dx.doi.org/10.1186/s13148-020-00987-2
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author Bao, Xiuqin
Zuo, Yangjin
Chen, Diyu
Zhao, Cunyou
author_facet Bao, Xiuqin
Zuo, Yangjin
Chen, Diyu
Zhao, Cunyou
author_sort Bao, Xiuqin
collection PubMed
description BACKGROUND: Reactivation of fetal hemoglobin (HbF, α(2)γ(2)) holds a therapeutic target for β-thalassemia and sickle cell disease. Although many HbF regulators have been identified, the methylation patterns in β-globin cluster driving the fetal-to-adult hemoglobin switch remains to be determined. RESULTS: Here, we evaluated DNA methylation patterns of the β-globin cluster from peripheral bloods of 105 β(0)/β(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 γ- and β-globin promoters displayed hypomethylation in β(0)/β(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 β(0)/β(0)-patients compared with normal controls; and methylation level of γ-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 β(0)-thalassemia patients. Finally, γ-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 β-globin cluster associated with β(0) thalassemia disease and γ-globin expression, contributed to understand the epigenetic modification in β(0) thalassemia patients and provided candidate targets for the therapies of β-hemoglobinopathies.
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spelling pubmed-77126192020-12-03 DNA methylation patterns of β-globin cluster in β-thalassemia patients Bao, Xiuqin Zuo, Yangjin Chen, Diyu Zhao, Cunyou Clin Epigenetics Research BACKGROUND: Reactivation of fetal hemoglobin (HbF, α(2)γ(2)) holds a therapeutic target for β-thalassemia and sickle cell disease. Although many HbF regulators have been identified, the methylation patterns in β-globin cluster driving the fetal-to-adult hemoglobin switch remains to be determined. RESULTS: Here, we evaluated DNA methylation patterns of the β-globin cluster from peripheral bloods of 105 β(0)/β(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 γ- and β-globin promoters displayed hypomethylation in β(0)/β(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 β(0)/β(0)-patients compared with normal controls; and methylation level of γ-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 β(0)-thalassemia patients. Finally, γ-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 β-globin cluster associated with β(0) thalassemia disease and γ-globin expression, contributed to understand the epigenetic modification in β(0) thalassemia patients and provided candidate targets for the therapies of β-hemoglobinopathies. BioMed Central 2020-12-03 /pmc/articles/PMC7712619/ /pubmed/33272312 http://dx.doi.org/10.1186/s13148-020-00987-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Bao, Xiuqin
Zuo, Yangjin
Chen, Diyu
Zhao, Cunyou
DNA methylation patterns of β-globin cluster in β-thalassemia patients
title DNA methylation patterns of β-globin cluster in β-thalassemia patients
title_full DNA methylation patterns of β-globin cluster in β-thalassemia patients
title_fullStr DNA methylation patterns of β-globin cluster in β-thalassemia patients
title_full_unstemmed DNA methylation patterns of β-globin cluster in β-thalassemia patients
title_short DNA methylation patterns of β-globin cluster in β-thalassemia patients
title_sort dna methylation patterns of β-globin cluster in β-thalassemia patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712619/
https://www.ncbi.nlm.nih.gov/pubmed/33272312
http://dx.doi.org/10.1186/s13148-020-00987-2
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