Author/Authors :
Dehghani Fard, Ali tarbiat modares university - Faculty of Medical Sciences - Department of Hematology and Blood Banking, تهران, ايران , Kaviani, Saeid tarbiat modares university - Faculty of Medical Sciences - Department of Hematology and Blood Banking, تهران, ايران , Noruzinia, Mehrdad tarbiat modares university - Faculty of Medical Sciences - Department of Medical Genetics, تهران, ايران , Soleimani, Masoud tarbiat modares university - Faculty of Medical Sciences - Department of Hematology and Blood Banking, تهران, ايران , Abroun, Saeid tarbiat modares university - Faculty of Medical Sciences - Department of Hematology and Blood Banking, تهران, ايران , Hajifathali, Abbas shahid beheshti university of medical sciences - Faculty of Medicine - Department of Hematology, تهران, ايران , Pourfathollah, Ali Akbar tarbiat modares university - Faculty of Medical Sciences - Department of Immunology, تهران, ايران , Mortazavi, Yousef zanjan university of medical sciences - Department of Pathology, ايران , Zonoubi, Zahra shahid beheshti university of medical sciences - Mahdiyeh Hospital - Department of Obstetrics and Gynecology, تهران, ايران , Ahmadvand, Mohammad zahedan university of medical sciences - Department of Laboratory Sciences, ايران , Shahjahani, Mohammad tarbiat modares university - Faculty of Medical Sciences - Department of Hematology and Blood Banking, تهران, ايران , Saki, Najmaldin ahvaz jundishapur university of medical sciences - Thalassemia and Hemoglobinopathy Research Center, اهواز, ايران , Farshdusti Hagh, Majid tabriz university of medical sciences - Division of Laboratory Hematology and Blood Banking, ايران
Abstract :
Background: Human β-like globin genes regula on during development from embyonic to adult stage results in genera on of different types of hemoglobin with different func ons. As β-thalassemia and sickle cell disease are disorders of β-globin chain, epigene c drugs such as thalidomide and sodium butyrate which can induce γ-globin gene are considered as a novel therapeu c approach. Drugs effec ve in decreasing DNA methyla on and altera on of histone methyla on pa$ern can result in γ-globin gene upregula on. Materials and Methods: This study was performed on erythroid progenitors derived from cord blood CD133+ cells. Erythroid progenitors were treated with thalidomide and sodium butyrate as single and combina on therapies in 10 μM concentra ons. Chroma n Immuno Percipita on (ChIP) assay was used to evaluate the change in H3K27 methyla on pa$ern. Also, Real- me PCR assay was used to compare the number of DNA fragments resul ng from immunoprecipita on in different drug treatment groups. Results: Real- me PCR assay indicated considerable effect of thalidomide single therapy in decreasing H3K27 methyla on compared with sodium butyrate and combina on therapy. Conclusion: According to the results of this study, it seems that the synergis c effect of thalidomide and sodium butyrate combina on therapy on γ-globin gene induc on arises from other epigene c mechanisms
Keywords :
Epigenesis , Genetic , thalidomide , sodium butyrate , methylation
