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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3136-3142. Prepublished online as a Blood First Edition Paper on August 1, 2007; DOI 10.1182/blood-2007-03-080291. This Article Full Text (PDF) All Versions of this Article: blood-2007-03-080291v1 110/9/3136    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 Yeamans, C. Articles by Friedman, A. D. Search for Related Content PubMed PubMed Citation Articles by Yeamans, C. Articles by Friedman, A. D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 15, 2007 Accepted July 26, 2007 C/EBP binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment Christine Yeamans, Dehua Wang, Ido Paz-Priel, Bruce E. Torbett, Daniel G. Tenen, and Alan D. Friedman* Division of Pediatric Oncology, Johns Hopkins University, Baltimore, MD, United States The Scripps Research Institute, La Jolla, CA, United States Harvard Institutes of Medicine, Boston, MA, United States * Corresponding author; email: afriedm2{at}jhmi.edu. The PU.1 gene contains a 237 base pair distal enhancer located 14 kilobases upstream of its promoter. We have identified two sites within the PU.1 enhancer that strongly bind C/EBP in a gel shift assay, and interaction with endogenous C/EBP was confirmed by chromatin immunoprecipitation. Mutation of these DNA elements reduced activity of a distal enhancer-promoter construct 2- or 5-fold in a myeloid cell line, while mutation of a weaker C/EBP-binding site located in the promoter minimally reduced activity in this context. These findings strengthen the link between C/EBP and PU.1 expression. Reduction of C/EBP activity in cases of acute myeloid leukemia may therefore contribute to transformation by reducing PU.1 levels. In addition, induction of PU.1 by C/EBP during normal hematopoiesis may contribute to stem cell commitment to the myeloid lineages and further commitment to monopoiesis. Consistent with a requirement for C/EBP induction of PU.1 during myeloid development, we demonstrate that C/EBP induces monocytic development when expressed in PU.1(+/+), PU.1(+/-), or PU.1(+/kd) marrow myeloid progenitors but induces granulocyte lineage commitment in PU.1(kd/kd) cells lacking the PU.1 distal enhancer and does not induce either lineage in PU.1(-/-) cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Tissieres, T. Araud, A. Ochoda, G. Drifte, I. Dunn-Siegrist, and J. Pugin Cooperation between PU.1 and CAAT/Enhancer-binding Protein {beta} Is Necessary to Induce the Expression of the MD-2 Gene J. Biol. Chem., September 25, 2009; 284(39): 26261 - 26272. [Abstract] [Full Text] [PDF] G. D. Jack, L. Zhang, and A. D. Friedman M-CSF elevates c-Fos and phospho-C/EBP{alpha}(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification Blood, September 3, 2009; 114(10): 2172 - 2180. [Abstract] [Full Text] [PDF] M. Hoogenkamp, M. Lichtinger, H. Krysinska, C. Lancrin, D. Clarke, A. Williamson, L. Mazzarella, R. Ingram, H. Jorgensen, A. Fisher, et al. Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program Blood, July 9, 2009; 114(2): 299 - 309. [Abstract] [Full Text] [PDF] T. Ito, C. Nishiyama, N. Nakano, M. Nishiyama, Y. Usui, K. Takeda, S. Kanada, K. Fukuyama, H. Akiba, T. Tokura, et al. Roles of PU.1 in monocyte- and mast cell-specific gene regulation: PU.1 transactivates CIITA pIV in cooperation with IFN-{gamma} Int. Immunol., July 1, 2009; 21(7): 803 - 816. [Abstract] [Full Text] [PDF] M. Pata, C. Heraud, and J. Vacher OSTM1 Bone Defect Reveals an Intercellular Hematopoietic Crosstalk J. Biol. Chem., November 7, 2008; 283(45): 30522 - 30530. [Abstract] [Full Text] [PDF] A. R. Soliera, M. R. Lidonnici, G. Ferrari-Amorotti, M. Prisco, Y. Zhang, R. V. Martinez, N. J. Donato, and B. Calabretta Transcriptional repression of c-Myb and GATA-2 is involved in the biologic effects of C/EBP{alpha} in p210BCR/ABL-expressing cells Blood, September 1, 2008; 112(5): 1942 - 1950. [Abstract] [Full Text] [PDF] M. Hoogenkamp, H. Krysinska, R. Ingram, G. Huang, R. Barlow, D. Clarke, A. Ebralidze, P. Zhang, H. Tagoh, P. N. Cockerill, et al. The Pu.1 Locus Is Differentially Regulated at the Level of Chromatin Structure and Noncoding Transcription by Alternate Mechanisms at Distinct Developmental Stages of Hematopoiesis Mol. Cell. Biol., November 1, 2007; 27(21): 7425 - 7438. [Abstract] [Full Text] [PDF]

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