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Blood, 5 February 2009, Vol. 113, No. 6, pp. 1340-1349. Prepublished online as a Blood First Edition Paper on October 21, 2008; DOI 10.1182/blood-2008-08-174854. This Article Full Text (PDF) Supplemental Tables and Figures Additional Supplemental Figures All Versions of this Article: blood-2008-08-174854v1 113/6/1340    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles via Google Scholar Google Scholar Articles by Fu, Y.-F. Articles by Liu, T. X. Search for Related Content PubMed PubMed Citation Articles by Fu, Y.-F. Articles by Liu, T. X. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 18, 2008 Accepted September 27, 2008 Mir-144 selectively regulates embryonic -hemoglobin synthesis during primitive erythropoiesis Yan-Fang Fu, Ting-Ting Du, Mei Dong, Kang-Yong Zhu, Chang-Bin Jing, Yong Zhang, Lei Wang, Hong-Bo Fan, Yi Chen, Yi Jin, Gui-Ping Yue, Sai-Juan Chen, Zhu Chen, Qiu-Hua Huang, Qing Jing, Min Deng, and Ting Xi Liu* Laboratory of Development and Diseases and State Key Laboratory for Medical Genomics, Institute of Health Sciences (IHS), Shanghai, China State Key Laboratory for Medical Genomics, Institute of Health Sciences (IHS), Shanghai, China Laboratory of Nucleic Acid and Molecular Biomedicine, Institute of Health Sciences (IHS), Shanghai, China Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China Model Organism Division, E-Institutes of Shanghai Universities, Shanghai, China * Corresponding author; email: txliu{at}sibs.ac.cn. Precise transcriptional control of developmental stage-specific expression and switching of - and -globin genes is significantly important to understand the general principles controlling gene expression and the pathogenesis of thalassemia. Although transcription factors regulating -globin genes have been identified, little is known about the microRNAs and trans-acting mechanism controlling -globin genes transcription. Here, we show that an erythroid lineage-specific microRNA gene, miR-144, expressed at specific developmental stages during zebrafish embryogenesis, negatively regulates the embryonic -globin, but not embryonic -globin genes expression, through physiologically targeting klfd, an erythroid-specific Kruppel-like transcription factor. Klfd selectively binds to the CACCC boxes in the promoters of both -globin and miR-144 genes to activate their transcriptions, thus forming a negative feedback circuitry to fine-tune the expression of embryonic -globin gene. The selective effect of miR-144-Klfd pathway on globin gene regulation may thereby constitute a novel therapeutic target for improving the clinical outcome of patients with thalassemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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