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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4302-4309. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-01-0107. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2003-01-0107v1 103/11/4302    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhou, G.-P. Articles by Gallagher, P. G Search for Related Content PubMed PubMed Citation Articles by Zhou, G.-P. Articles by Gallagher, P. G Social Bookmarking                   What's this? Submitted January 14, 2003 Accepted February 2, 2004 The Human Potassium-Chloride Cotransporter 1 (KCC1, SLC12A4) Promoter is Regulated by AP-2 and Contains a Functional Downstream Promoter Element (DPE) Guo-Ping Zhou, Clara Wong, Robert Su, Scott C Crable, Kathleen P Anderson, and Patrick G Gallagher* Pediatrics, Yale University, New Haven, CT, USA Pediatrics, Cincinnati Children's Hospital, Cincinnati, OH, USA * Corresponding author; email: patrick.gallagher{at}yale.edu. The majority of K-Cl cotransport in the erythrocyte is attributed to KCC1. K-Cl cotransport is elevated in sickle erythrocytes and the KCC1 gene has been proposed as a modifier gene in sickle cell disease. To provide insight into our understanding of the regulation of the human KCC1 gene, we mapped the 5' end of the KCC1 cDNA, cloned the corresponding genomic DNA, and identified the KCC1 gene promoter. The core promoter lacks a TATA-box and is composed of an initiator element (InR) and a downstream promoter element (DPE), a combination found primarily in Drosophila gene promoters and rarely observed in mammalian gene promoters. Mutational analyses demonstrated that both the InR and DPE sites were critical for full promoter activity. In vitro DNAse I foot printing, electrophoretic mobility shift assays, and reporter gene assays identified functional AP-2- and Sp1 sites in this region. The KCC1 promoter was transactivated by forced expression of AP-2 in heterologous cells. Sequences encoding the InR, DPE, AP-2 and Sp1 sites were 100% conserved between human and murine KCC1 genes. In vivo studies using chromatin immunoprecipitation assays with anti-histone H3 and anti-histone H4 antibodies demonstrated hyperacetylation of this core promoter region. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Gamba Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters Physiol Rev, April 1, 2005; 85(2): 423 - 493. [Abstract] [Full Text] [PDF]

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