This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chyla, B. J.
Right arrow Articles by Hiebert, S. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chyla, B. J.
Right arrow Articles by Hiebert, S. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2008, p. 6234-6247, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00404-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Deletion of Mtg16, a Target of t(16;21), Alters Hematopoietic Progenitor Cell Proliferation and Lineage Allocation{triangledown} ,{dagger}

Brenda J. Chyla,1,{ddagger},§ Isabel Moreno-Miralles,1,{ddagger},¶ Melissa A. Steapleton,1,{ddagger} Mary Ann Thompson,2,3 Srividya Bhaskara,1 Michael Engel,1,4 and Scott W. Hiebert1,2*

Department of Biochemistry,1 Vanderbilt-Ingram Cancer Center,2 Department of Pathology,3 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 372324

Received 10 March 2008/ Returned for modification 5 May 2008/ Accepted 7 August 2008

While a number of DNA binding transcription factors have been identified that control hematopoietic cell fate decisions, only a limited number of transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and the nuclear hormone corepressor [N-CoR]) have been linked to these functions. Here, we show that the transcriptional corepressor Mtg16 (myeloid translocation gene on chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, is required for hematopoietic progenitor cell fate decisions and for early progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid progenitor cells toward the granulocytic/macrophage lineage while reducing the numbers of megakaryocyte-erythroid progenitor cells. In addition, inactivation of Mtg16 impaired the rapid expansion of short-term stem cells, multipotent progenitor cells, and megakaryocyte-erythroid progenitor cells that is required under hematopoietic stress/emergency. This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16–/– defect.

* Corresponding author. Mailing address: Department of Biochemistry, 512 Preston Research Building, Vanderbilt University School of Medicine, 23rd and Pierce Ave., Nashville, TN 37232. Phone: (615) 936-3582. Fax: (615) 936-1790. E-mail: scott.hiebert{at}vanderbilt.edu

{triangledown} Published ahead of print on 18 August 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this study.

§ Present address: Abbott Laboratories, Abbott Park, IL.

Present address: University of North Carolina, Chapel Hill, NC.

Molecular and Cellular Biology, October 2008, p. 6234-6247, Vol. 28, No. 20
0270-7306/08/$08.00+0     doi:10.1128/MCB.00404-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Guo, C., Hu, Q., Yan, C., Zhang, J. (2009). Multivalent Binding of the ETO Corepressor to E Proteins Facilitates Dual Repression Controls Targeting Chromatin and the Basal Transcription Machinery. Mol. Cell. Biol. 29: 2644-2657 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»