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Blood, 1 December 2003, Vol. 102, No. 12, pp. 4214-4222. Prepublished online as a Blood First Edition Paper on August 14, 2003; DOI 10.1182/blood-2002-12-3766. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3766v1 102/12/4214    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 Dempsey, N. J. Articles by Little, J. A. Search for Related Content PubMed PubMed Citation Articles by Dempsey, N. J. Articles by Little, J. A. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Induction of an embryonic globin gene promoter by short-chain fatty acids Nancy J. Dempsey, Laureen S. Ojalvo, Davina W. Wu, and Jane A. Little From Hematology, Oncology, and Transplantation, Department of Internal Medicine, University of Minnesota, Minneapolis, MN; and Laboratory of Cellular and Developmental Biology (LCDB), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD. Short-chain fatty acids (SCFAs) and dimethyl sulfoxide (DMSO) induce adult erythroid differentiation in murine erythroleukemia (MEL) cells, but only SCFAs concurrently up-regulate expression from the endogenous embryonic globin gene y. The y promoter, linked to a reporter gene and stably transfected into MEL cells, was tested during adult erythroid differentiation. Both the y-CACCC site at -114 bp and enhancer sequences (hypersensitive site 2 [HS2]) from the -globin locus control region (LCR) were essential to maximal SCFA-mediated induction of expression from these constructs in MEL cells. Gel-shift analyses of binding activity from SCFA-induced MEL cell nuclear extracts showed in vitro binding by specificity proteins 1 and 3 (SP1, SP3) and basic or erythroid Krüppel-like factors (BKLF, EKLF) at the y-CACCC site. In a functional analysis, transient cotransfections in nonerythroid NIH/3T3 cells of SP1, SP3, BKLF, or EKLF and HS2 y promoter-luciferase constructs, with or without coactivators (p300, CREB-binding protein [CBP], or p300/CBP-associated factor [PCAF]) and SCFAs, were performed. SP1, SP3, and EKLF further increased expression from HS2 y promoter constructs following exposure to SCFAs. This effect was variably augmented by coactivators and was diminished in EKLF mutants that were unable to undergo histone/factor-acetyl transferase (H/FAT)-mediated acetylation. In addition, acetylation of SP1 was detectable in NIH/3T3 cells following exposure to SCFAs. In sum, LCR sequence and an embryonic globin gene promoter CACCC site were essential to that promoter's up-regulation during SCFA-mediated induction of adult erythroid differentiation in vitro. Of factors that interact at the CACCC site, SCFA-mediated acetylation is implicated in SP1 and EKLF, and may be a mechanism through which SCFAs induce embryonic/fetal globin gene promoters during adult erythroid differentiation. (Blood. 2003;102:4214-4222) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Huang, S. Zhao, S. Ammanamanchi, M. Brattain, K. Venkatasubbarao, and J. W. Freeman Trichostatin A Induces Transforming Growth Factor {beta} Type II Receptor Promoter Activity and Acetylation of Sp1 by Recruitment of PCAF/p300 to a Sp1{middle dot}NF-Y Complex J. Biol. Chem., March 18, 2005; 280(11): 10047 - 10054. [Abstract] [Full Text] [PDF]

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