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Blood, 15 January 2009, Vol. 113, No. 3, pp. 505-516. Prepublished online as a Blood First Edition Paper on September 25, 2008; DOI 10.1182/blood-2008-01-136218. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-136218v1 113/3/505    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 Zhao, H. Articles by Gewirtz, A. M. Search for Related Content PubMed PubMed Citation Articles by Zhao, H. Articles by Gewirtz, A. M. Related Collections Hematopoiesis and Stem Cells Plenary Papers Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory feedback loop in human hematopoietic cells Huiwu Zhao1, Anna Kalota1, Shenghao Jin1, and Alan M. Gewirtz1 1 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia The c-myb proto-oncogene encodes an obligate hematopoietic cell transcription factor important for lineage commitment, proliferation, and differentiation. Given its critical functions, c-Myb regulatory factors are of great interest but remain incompletely defined. Herein we show that c-Myb expression is subject to posttranscriptional regulation by microRNA (miRNA)–15a. Using a luciferase reporter assay, we found that miR-15a directly binds the 3'-UTR of c-myb mRNA. By transfecting K562 myeloid leukemia cells with a miR-15a mimic, functionality of binding was shown. The mimic decreased c-Myb expression, and blocked the cells in the G1 phase of cell cycle. Exogenous expression of c-myb mRNA lacking the 3'-UTR partially rescued the miR-15a induced cell-cycle block. Of interest, the miR-15a promoter contained several potential c-Myb protein binding sites. Occupancy of one canonical c-Myb binding site was demonstrated by chromatin immunoprecipitation analysis and shown to be required for miR-15a expression in K562 cells. Finally, in studies using normal human CD34+ cells, we showed that c-Myb and miR-15a expression were inversely correlated in cells undergoing erythroid differentiation, and that overexpression of miR-15a blocked both erythroid and myeloid colony formation in vitro. In aggregate, these findings suggest the presence of a c-Myb–miR-15a autoregulatory feedback loop of potential importance in human hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MYB and miR: a pair well matched Marc A. Kerenyi and Ernst W. Müllner Blood 2009 113: 499-500. [Full Text] [PDF] This article has been cited by other articles: M. Persson, Y. Andren, J. Mark, H. M. Horlings, F. Persson, and G. Stenman Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck PNAS, November 3, 2009; 106(44): 18740 - 18744. [Abstract] [Full Text] [PDF] F. Navarro, D. Gutman, E. Meire, M. Caceres, I. Rigoutsos, Z. Bentwich, and J. Lieberman miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53 Blood, September 3, 2009; 114(10): 2181 - 2192. [Abstract] [Full Text] [PDF] N. Felli, F. Pedini, P. Romania, M. Biffoni, O. Morsilli, G. Castelli, S. Santoro, S. Chicarella, A. Sorrentino, C. Peschle, et al. MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis Haematologica, April 1, 2009; 94(4): 479 - 486. [Abstract] [Full Text] [PDF]

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