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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4078-4083. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-09-3231. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3231v1 103/11/4078    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 Xue, L. Articles by Bieker, J. J. Search for Related Content PubMed PubMed Citation Articles by Xue, L. Articles by Bieker, J. J. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Regulatory elements of the EKLF gene that direct erythroid cell-specific expression during mammalian development Li Xue, Xiaoyong Chen, Yanjie Chang, and James J. Bieker From the Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY. Erythroid Krüppel-like factor (EKLF) plays an essential role in enabling -globin expression during erythroid ontogeny. It is first expressed in the extraembryonic mesoderm of the yolk sac within the morphologically unique cells that give rise to the blood islands, and then later within the hepatic primordia. The BMP4/Smad pathway plays a critical role in the induction of EKLF, and transient transfection analyses demonstrate that sequences located within less than 1 kb of its transcription initiation site are sufficient for high-level erythroid-specific transcription. We have used transgenic analyses to verify that 950 bp located adjacent to the EKLF start site of transcription is sufficient to generate lacZ expression within the blood islands as well as the fetal liver during embryonic development. Of particular importance are 3 regions, 2 of which overlap endogenous erythroid-specific DNase hypersensitive sites, and 1 of which includes the proximal promoter region. The onset of transgene expression mimics that of endogenous EKLF as it begins by day 7.5 (d7.5) to d8.0. In addition, it exhibits a strict hematopoietic specificity, localized only to these cells and not to the adjacent vasculature at all stages examined. Finally, expression is heterocellular, implying that although these elements are sufficient for tissue-specific expression, they do not shield against the position effects of adjacent chromatin. These analyses demonstrate that a surprisingly small DNA segment contains all the information needed to target a linked gene to the hematopoietic compartment at both early and later stages of development, and may be a useful cassette for this purpose. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Lohmann and J. J. Bieker Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment Development, June 15, 2008; 135(12): 2071 - 2082. [Abstract] [Full Text] [PDF] E. Delabesse, S. Ogilvy, M. A. Chapman, S. G. Piltz, B. Gottgens, and A. R. Green Transcriptional Regulation of the SCL Locus: Identification of an Enhancer That Targets the Primitive Erythroid Lineage In Vivo Mol. Cell. Biol., June 15, 2005; 25(12): 5215 - 5225. [Abstract] [Full Text] [PDF] M. Nakano, K. Ohneda, H. Yamamoto-Mukai, R. Shimizu, O. Ohneda, S. Ohmura, M. Suzuki, S. Tsukamoto, T. Yanagawa, H. Yoshida, et al. Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells Genes Cells, January 1, 2005; 10(1): 47 - 62. [Abstract] [Full Text] [PDF]

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