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Blood, 10 September 2009, Vol. 114, No. 11, pp. 2299-2306. Prepublished online as a Blood First Edition Paper on July 13, 2009; DOI 10.1182/blood-2009-05-219386. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-05-219386v1 114/11/2299    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Sripichai, O. Articles by Miller, J. L. PubMed PubMed Citation Articles by Sripichai, O. Articles by Miller, J. L. Related Collections Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming Orapan Sripichai1,*, Christine M. Kiefer2,*, Natarajan V. Bhanu1,*, Toshihiko Tanno1, Seung-Jae Noh1, Sung-Ho Goh1, J. Eric Russell3, Cheryl L. Rognerud4, Ching-Nan Ou4, Patricia A. Oneal1, Emily R. Meier1, Nicole M. Gantt1, Colleen Byrnes1, Y. Terry Lee1, Ann Dean2, and Jeffery L. Miller1 1 Molecular Medicine Branch and 2 Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; 3 Department of Medicine (Hematology-Oncology), University of Pennsylvania School of Medicine and the Children's Hospital of Philadelphia, Philadelphia; and 4 Department of Pathology, Texas Children's Hospital and Baylor College of Medicine, Houston Therapeutic regulation of globin genes is a primary goal of translational research aimed toward hemoglobinopathies. Signal transduction was used to identify chromatin modifications and transcription factor expression patterns that are associated with globin gene regulation. Histone modification and transcriptome profiling were performed using adult primary CD34+ cells cultured with cytokine combinations that produced low versus high levels of gamma-globin mRNA and fetal hemoglobin (HbF). Embryonic, fetal, and adult globin transcript and protein expression patterns were determined for comparison. Chromatin immunoprecipitation assays revealed RNA polymerase II occupancy and histone tail modifications consistent with transcriptional activation only in the high-HbF culture condition. Transcriptome profiling studies demonstrated reproducible changes in expression of nuclear transcription factors associated with high HbF. Among the 13 genes that demonstrated differential transcript levels, 8 demonstrated nuclear protein expression levels that were significantly changed by cytokine signal transduction. Five of the 8 genes are recognized regulators of erythropoiesis or globin genes (MAFF, ID2, HHEX, SOX6, and EGR1). Thus, cytokine-mediated signal transduction in adult erythroid cells causes significant changes in the pattern of globin gene and protein expression that are associated with distinct histone modifications as well as nuclear reprogramming of erythroid transcription factors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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