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Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
BACKGROUND: Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599103/ https://www.ncbi.nlm.nih.gov/pubmed/23316703 http://dx.doi.org/10.1186/1479-5876-11-14 |
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author | He, Yinghong Rank, Gerhard Zhang, Miaomiao Ju, Junyi Liu, Ronghua Xu, Zhen Brown, Fiona Cerruti, Loretta Ma, Chi Tan, Renxiang Jane, Stephen M Zhao, Quan |
author_facet | He, Yinghong Rank, Gerhard Zhang, Miaomiao Ju, Junyi Liu, Ronghua Xu, Zhen Brown, Fiona Cerruti, Loretta Ma, Chi Tan, Renxiang Jane, Stephen M Zhao, Quan |
author_sort | He, Yinghong |
collection | PubMed |
description | BACKGROUND: Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells. METHODS: Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP). RESULTS: Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5). CONCLUSIONS: The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia. |
format | Online Article Text |
id | pubmed-3599103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35991032013-03-17 Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde He, Yinghong Rank, Gerhard Zhang, Miaomiao Ju, Junyi Liu, Ronghua Xu, Zhen Brown, Fiona Cerruti, Loretta Ma, Chi Tan, Renxiang Jane, Stephen M Zhao, Quan J Transl Med Research BACKGROUND: Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells. METHODS: Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP). RESULTS: Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5). CONCLUSIONS: The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia. BioMed Central 2013-01-14 /pmc/articles/PMC3599103/ /pubmed/23316703 http://dx.doi.org/10.1186/1479-5876-11-14 Text en Copyright ©2013 He et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research He, Yinghong Rank, Gerhard Zhang, Miaomiao Ju, Junyi Liu, Ronghua Xu, Zhen Brown, Fiona Cerruti, Loretta Ma, Chi Tan, Renxiang Jane, Stephen M Zhao, Quan Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
title | Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
title_full | Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
title_fullStr | Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
title_full_unstemmed | Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
title_short | Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
title_sort | induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599103/ https://www.ncbi.nlm.nih.gov/pubmed/23316703 http://dx.doi.org/10.1186/1479-5876-11-14 |
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