Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 1 October 2006, Vol. 108, No. 7, pp. 2198-2206.
Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-04-019760.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2006-04-019760v1
108/7/2198    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pang, L.
Right arrow Articles by Poncz, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pang, L.
Right arrow Articles by Poncz, M.
Related Collections
Right arrow Free Research Articles
Right arrow Hematopoiesis
Right arrow Hemostasis, Thrombosis, and Vascular Biology
Right arrowRelated Article in Blood Online
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

HEMATOPOIESIS

Maturation stage–specific regulation of megakaryopoiesis by pointed-domain Ets proteins

Liyan Pang, Hai-Hui Xue, Gabor Szalai, Xun Wang, Yuhuan Wang, Dennis K. Watson, Warren J. Leonard, Gerd A. Blobel, and Mortimer Poncz

From the Department of Pediatrics, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine; the Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD; the Departments of Pathology and Laboratory Medicine and Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston.

Numerous megakaryocyte-specific genes contain signature Ets-binding sites in their regulatory regions. Fli-1 (friend leukemia integration 1), an Ets transcription factor, is required for the normal maturation of megakaryocytes and controls the expression of multiple megakaryocyte-specific genes. However, in Fli-1–/– mice, early megakaryopoiesis persists, and the expression of the early megakaryocyte-specific genes, {alpha}IIb and cMpl, is maintained, consistent with functional compensation by a related Ets factor(s). Here we identify the Ets protein GABP{alpha} (GA-binding protein {alpha}) as a regulator of early megakaryocyte-specific genes. Notably, GABP{alpha} preferentially occupies Ets elements of early megakaryocyte-specific genes in vitro and in vivo, whereas Fli-1 binds both early and late megakaryocyte-specific genes. Moreover, the ratio of GABP{alpha}/Fli-1 expression declines throughout megakaryocyte maturation. Consistent with this expression pattern, primary fetal liver–derived megakaryocytes from Fli-1–deficient murine embryos exhibit reduced expression of genes associated with late stages of maturation (glycoprotein [GP] Ib{alpha}, GPIX, and platelet factor 4 [PF4]), whereas GABP{alpha}-deficient megakaryocytes were mostly impaired in the expression of early megakaryocyte-specific genes ({alpha}IIb and cMpl). Finally, mechanistic experiments revealed that GABP{alpha}, like Fli-1, can impart transcriptional synergy between the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 (friend of GATA-1). In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article in Blood Online:

Ets and megakaryocytes: maturation matters
Katya Ravid
Blood 2006 108: 2139. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 BloodHome page
G. A. Blobel
Kruppeling megakaryopoiesis
Blood, December 1, 2007; 110(12): 3823 - 3824.
[Full Text] [PDF]

Home page
 BloodHome page
A. G. Muntean, L. Pang, M. Poncz, S. F. Dowdy, G. A. Blobel, and J. D. Crispino
Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization
Blood, June 15, 2007; 109(12): 5199 - 5207.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
Sponsor: Genentech BioOncology and and Biogen Idec
Blood Online is supported in part by
Genentech BioOncology and Biogen Idec
  Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020