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Blood, 30 July 2009, Vol. 114, No. 5, pp. 983-994. Prepublished online as a Blood First Edition Paper on June 2, 2009; DOI 10.1182/blood-2009-03-207944. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2009-03-207944v1 114/5/983    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 Google Scholar Articles by Chou, S. T. Articles by Weiss, M. J. PubMed PubMed Citation Articles by Chou, S. T. Articles by Weiss, M. J. Related Collections Hematopoiesis and Stem Cells Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Graded repression of PU.1/Sfpi1 gene transcription by GATA factors regulates hematopoietic cell fate Stella T. Chou1, Eugene Khandros2, L. Charles Bailey3, Kim E. Nichols3, Christopher R. Vakoc4, Yu Yao1, Zan Huang5, John D. Crispino5, Ross C. Hardison6, Gerd A. Blobel1, and Mitchell J. Weiss1 1 Division of Hematology, The Children's Hospital of Philadelphia, PA; 2 Combined Degree Program and Cell and Molecular Biology Group, University of Pennsylvania, Philadelphia; 3 Division of Oncology, The Children's Hospital of Philadelphia, PA; 4 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; 5 Division of Hematology/Oncology, Northwestern University, Chicago, IL; and 6 Center for Comparative Genomics and Bioinformatics, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park GATA-1 and PU.1 are essential hematopoietic transcription factors that control erythromegakaryocytic and myelolymphoid differentiation, respectively. These proteins antagonize each other through direct physical interaction to repress alternate lineage programs. We used immortalized Gata1– erythromegakaryocytic progenitor cells to study how PU.1/Sfpi1 expression is regulated by GATA-1 and GATA-2, a related factor that is normally expressed at earlier stages of hematopoiesis. Both GATA factors bind the PU.1/Sfpi1 gene at 2 highly conserved regions. In the absence of GATA-1, GATA-2 binding is associated with an undifferentiated state, intermediate level PU.1/Sfpi1 expression, and low-level expression of its downstream myeloid target genes. Restoration of GATA-1 function induces erythromegakaryocytic differentiation. Concomitantly, GATA-1 replaces GATA-2 at the PU.1/Sfpi1 locus and PU.1/Sfpi1 expression is extinguished. In contrast, when GATA-1 is not present, shRNA knockdown of GATA-2 increases PU.1/Sfpi1 expression by 3-fold and reprograms the cells to become macrophages. Our findings indicate that GATA factors act sequentially to regulate lineage determination during hematopoiesis, in part by exerting variable repressive effects at the PU.1/Sfpi1 locus. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. D. Amigo, G. E. Ackermann, J. J. Cope, M. Yu, J. D. Cooney, D. Ma, N. B. Langer, E. Shafizadeh, G. C. Shaw, W. Horsely, et al. The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish Blood, November 19, 2009; 114(21): 4654 - 4663. [Abstract] [Full Text] [PDF]

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