Changing Pattern of Histone H3 Methylation following treatment of erythroid progenitors derived from cord blood CD133+ cells with sodium butyrate and thalidomide
Journal Title: Iranian Journal of Blood and Cancer - Year 2012, Vol 4, Issue 2
Abstract
Background: Human β-like globin genes regulaon during development from embyonic to adult stage results in generaon of different types of hemoglobin with different funcons. As β-thalassemia and sickle cell disease are disorders of β-globin chain, epigenec drugs such as thalidomide and sodium butyrate which can induce γ-globin gene are considered as a novel therapeuc approach. Drugs effecve in decreasing DNA methylaon and alteraon of histone methylaon pa$ern can result in γ-globin gene upregulaon. Materials and Methods: This study was performed on erythroid progenitors derived from cord blood CD133+ cells. Erythroid progenitors were treated with thalidomide and sodium butyrate as single and combinaon therapies in 10 μM concentraons. Chroman Immuno Percipitaon (ChIP) assay was used to evaluate the change in H3K27 methylaon pa$ern. Also, Real-me PCR assay was used to compare the number of DNA fragments resulng from immunoprecipitaon in different drug treatment groups. Results: Real-me PCR assay indicated considerable effect of thalidomide single therapy in decreasing H3K27 methylaon compared with sodium butyrate and combinaon therapy. Conclusion: According to the results of this study, it seems that the synergisc effect of thalidomide and sodium butyrate combinaon therapy on γ-globin gene inducon arises from other epigenec mechanisms.
Authors and Affiliations
Ali Dehghani Fard, Saeid Kaviani, Mehrdad Noruzinia, Masoud Soleimani, Abbas Hajifathali, Ali Akbar Pourfathollah, Yousef Mortazavi, Zahra Zonoubi, Mohammad Ahmadvand, Najmaldin Saki, Majid Farshdusti Hagh
Keywords
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