SEARCH:   Advanced

Blood, 15 November 2006, Vol. 108, No. 10, pp. 3590-3599. Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-01-023713. This Article Full Text (PDF) All Versions of this Article: blood-2006-01-023713v1 108/10/3590    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 Sangerman, J. Articles by Pace, B. S Search for Related Content PubMed PubMed Citation Articles by Sangerman, J. Articles by Pace, B. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 11, 2006 Accepted July 4, 2006 Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves -globin activation by CREB1 and ATF-2 Jose Sangerman, Moo Seung Lee, Xiao Yao, Eugene Oteng, Cheng-Hui Hsiao, Wei Li, Sima Zein, Solomon F Ofori-Acquah, and Betty S Pace* Yale University, Department of Pediatrics, Yale University, New Haven, CT, USA University of Texas at Dallas, Department of Molecular and Cell Biology, Richardson, TX, USA University of South Alabama, Department of Cell Biology and Neuroscience, Mobile, AL, USA * Corresponding author; email: bpace{at}utdallas.edu. The histone deacetylase inhibitors (HDACIs) butyrate and trichostatin A activate -globin expression via a p38 mitogen activating protein kinase-dependent mechanism. We hypothesized that downstream effectors of p38 MAPK, namely activating transcription factor-2 (ATF-2) and cyclic AMP response element (CRE) binding protein (CREB) are intimately involved in fetal hemoglobin induction by these agents. In this study, we observed increased ATF-2 and CREB1 phosphorylation mediated by the HDACIs in K562 cells, in conjunction with histone H4 hyperacetylation. Moreover, enhanced DNA-protein interactions occurred in the CRE in the G-globin promoter (G-CRE) in vitro after drug treatments; subsequent chromatin immunoprecipitation assays confirmed ATF-2 and CREB1 binding to the G-CRE in vivo. Enforced expression of ATF-2 and CREB produced G-promoter trans-activation which was abolished by a two base pair mutation in the putative G-CRE. The data presented herein demonstrates that -gene induction by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T.-F. Lou, M. Singh, A. Mackie, W. Li, and B. S. Pace Hydroxyurea Generates Nitric Oxide in Human Erythroid Cells: Mechanisms for {gamma}-Globin Gene Activation Experimental Biology and Medicine, November 1, 2009; 234(11): 1374 - 1382. [Abstract] [Full Text] [PDF] S.-Y. Park, J. H. Cho, D.-Y. Oh, J.-W. Park, M.-J. Ahn, J.-S. Han, and J.-W. Oh House Dust Mite Allergen Der f 2-induced Phospholipase D1 Activation Is Critical for the Production of Interleukin-13 through Activating Transcription Factor-2 Activation in Human Bronchial Epithelial Cells J. Biol. Chem., July 24, 2009; 284(30): 20099 - 20110. [Abstract] [Full Text] [PDF] H. Bhatia, J. L. Hallock, A. Dutta, S. Karkashon, L. S. Sterner, T. Miyazaki, A. Dean, and J. A. Little Short-chain fatty acid-mediated effects on erythropoiesis in primary definitive erythroid cells Blood, June 18, 2009; 113(25): 6440 - 6448. [Abstract] [Full Text] [PDF] S. Kodeboyina, S. Zein, M. Lee, P. Balamurugan, X. Yao, and B. Pace Role of Cjun in G{gamma}-Globin Gene Trans-Activation. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1870 - 1870. [Abstract] W. Aerbajinai, J. Zhu, Z. Gao, K. Chin, and G. P. Rodgers Thalidomide induces {gamma}-globin gene expression through increased reactive oxygen species mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis Blood, October 15, 2007; 110(8): 2864 - 2871. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020