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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5223-5232. Prepublished online as a Blood First Edition Paper on January 17, 2008; DOI 10.1182/blood-2007-10-115857. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2007-10-115857v1 111/10/5223    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Obara, N. Articles by Yamamoto, M. Search for Related Content PubMed PubMed Citation Articles by Obara, N. Articles by Yamamoto, M. Related Collections Red Cells Gene Expression Chemokines, Cytokines, and Interleukins Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Repression via the GATA box is essential for tissue-specific erythropoietin gene expression Naoshi Obara*,1,2, Norio Suzuki*,1,3, Kibom Kim13, Toshiro Nagasawa2, Shigehiko Imagawa2, and Masayuki Yamamoto14 1 Center for Tsukuba Advanced Research Alliance (TARA), 2 Graduate School of Comprehensive Human Sciences (CHS), and 3 Exploratory Research for Advanced Technology (ERATO), Environmental Response Project, Japan Science and Technology Agency (JST), University of Tsukuba, Tsukuba; and 4 Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan In response to anemia, erythropoietin (Epo) gene transcription is markedly induced in the kidney and liver. To elucidate how Epo gene expression is regulated in vivo, we established transgenic mouse lines expressing green fluorescent protein (GFP) under the control of a 180-kb mouse Epo gene locus. GFP expression was induced by anemia or hypoxia specifically in peritubular interstitial cells of the kidney and hepatocytes surrounding the central vein. Surprisingly, renal Epo-producing cells had a neuronlike morphology and expressed neuronal marker genes. Furthermore, the regulatory mechanisms of Epo gene expression were explored using transgenes containing mutations in the GATA motif of the promoter region. A single nucleotide mutation in this motif resulted in constitutive ectopic expression of transgenic GFP in renal distal tubules, collecting ducts, and certain populations of epithelial cells in other tissues. Since both GATA-2 and GATA-3 bind to the GATA box in distal tubular cells, both factors are likely to repress constitutively ectopic Epo gene expression in these cells. Thus, GATA-based repression is essential for the inducible and cell type–specific expression of the Epo gene. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Where the Epo cells are Constance Tom Noguchi Blood 2008 111: 4836-4837. [Full Text] [PDF] This article has been cited by other articles: T. Yamashita, O. Ohneda, A. Sakiyama, F. Iwata, K. Ohneda, and Y. Fujii-Kuriyama The microenvironment for erythropoiesis is regulated by HIF-2{alpha} through VCAM-1 in endothelial cells Blood, August 15, 2008; 112(4): 1482 - 1492. [Abstract] [Full Text] [PDF]

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