คลังข้อมูลการวิจัยการเกษตรไทย

ผู้แต่ง Woratree Kaewsakulthong

เผยแพร่โดย

1 Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand 2 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand 3 Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Canada 4 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 5 National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand

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งานวิจัยที่แนะนำ รูปแบบการเปลี่ยนแปลงฮีสโตนของเซลล์เม็ดเลือดแดงตัวอ่อนผู้ป่วยเบต้า-ธาลัสซีเมีย Histone Modification Profiles of β-Thalassemia Erythroblast Cells UNC0638 induces high levels of fetal hemoglobin expression in β-thalassemia/HbE erythroid progenitor cells Downregulation of transcription factor LRF/ZBTB7A increases fetal hemoglobin expression in -thalassemia/hemoglobin E erythroid cells Qualitative and quantitative comparison of the proteome of erythroid cells differentiated from human iPSCs and adult erythroid cells by multiplex TMT labelling and nanoLC-MS/MS การประกันคุณภาพทางห้องปฏิบัติการด้านโมเลกุลธาลัสซีเมีย Proficiency Testing Programme in Molecular Thalassemia detection Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects Comparison of gene expression profiles between human erythroid cells derived from fetal liver and adult peripheral blood Development of fetal hemoglobin inducers from medicinal plants for the clinical management of beta-thalassemia Generation of porcine induced-pluripotent stem cells from Sertoli cells High-level induction of fetal haemoglobin by pomalidomide in β-thalassaemia/HbE erythroid progenitor cells

คัดลอก URL

ชื่อเรื่อง (EN):	Histone modification levels in β-thalassemia/hemoglobin E erythroid cells
ผู้แต่ง / หัวหน้าโครงการ (EN):	Woratree Kaewsakulthong
บทคัดย่อ (EN):	Background: β-Thalassemia/hemoglobin E (HbE) disease represent a half of the clinically severe β-thalassemia worldwide, with highest incidence in Southeast Asia. Despite similar genetic backgrounds, patients show remarkable phenotypic diversity ranging from nearly asymptomatic to transfusion-dependent anemia with complications. The reason underlying this clinical heterogeneity remain largely obscure. In this study, we hypothesize that epigenetic factors contribute to modification of chromatin structure at the globin genes and are responsible for deregulation of globin gene expression and β-thalassemia/HbE disease severity. Materials and Methods: An in vitro erythroid culture was carried out in CD34+ progenitor cells derived from β-thalassemia/HbE patients presenting mildly- and severely-affected clinical symptoms, and normal donors. Genome-wide analysis of histone modifications was studied by native chromatin immunoprecipitation (ChIP) followed by deep sequencing of active and repressive histone marks including H3K4me1, H3K4me3, H3K27ac and H3K27me3. Results: The β-thalassemia/HbE erythroid cells exhibited enhanced proliferation but impaired terminal erythroid maturation. The level of fetal hemoglobin (HbF) vary from 24% to 62% with average of 37.9+10.8 (n=15). We found an increase in the repressive histone mask H3K27me3 and decrease of the active histone mark H3K27ac and H3K4me3 at the β-globin promoter of the erythroid cells derived from severe-affected β-thalassemia/HbE patients. Discussion and conclusion: Histone modification levels correlate with the diminished levels of β-globin gene expression in β-thalassemia/HbE erythroid cells. The study deciphered a molecular mechanism by which the globin genes are regulate in β-thalassemia/HbE erythroid cells and identify new candidate epigenetic marks associated with the severity of the disease.
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ภาษา (EN):	en
เอกสารแนบ (EN):	http://nih.dmsc.moph.go.th/research/showimgdetil.php?id=682
เผยแพร่โดย (EN):	1 Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand 2 Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand 3 Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Canada 4 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 5 National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand
คำสำคัญ (EN):	ChIP
เจ้าของลิขสิทธิ์ (EN):	National Institute of Health, Department of Medical Science