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

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 15 January 2007, Vol. 109, No. 2, pp. 795-801.
Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-06-027946.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2006-06-027946v1
109/2/795    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 He, Z.
Right arrow Articles by Russell, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by He, Z.
Right arrow Articles by Russell, J. E.
Related Collections
Right arrow Red Cells
Right arrow Gene Expression
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

RED CELLS

Dynamic posttranscriptional regulation of {epsilon}-globin gene expression in vivo

Zhenning He1, and J. Eric Russell1,2,

1 Department of Medicine (Hematology-Oncology) and 2 Department of Pediatrics (Hematology), University of Pennsylvania School of Medicine, and The Children's Hospital of Philadelphia, PA

Functional studies of embryonic {epsilon}-globin indicate that individuals with ß thalassemia or sickle cell disease are likely to benefit from therapeutic, transcriptional derepression of its encoding gene. The success of {epsilon}-globin gene-reactivation strategies, however, will be tempered by the stability that {epsilon}-globin mRNA exhibits in developmental stage-discordant definitive erythroid progenitors. Using cell culture and transgenic mouse model systems, we demonstrate that {epsilon}-globin mRNA is modestly unstable in immature, transcriptionally active erythroid cells, but that this characteristic has relatively little impact on the accumulation of {epsilon}-globin mRNA at subsequent stages of terminal differentiation. Importantly, the constitutive stability of {epsilon}-globin mRNA increases in transgenic mouse models of ß thalassemia, suggesting that {epsilon}- and ß-globin mRNAs are coregulated through a shared posttranscriptional mechanism. As anticipated, relevant cis-acting determinants of {epsilon}-globin mRNA stability map to its 3' UTR, consistent with the positioning of functionally related elements in other globin mRNAs. These studies demonstrate that posttranscriptional processes do not pose a significant practical barrier to {epsilon}-globin gene reactivation and, moreover, indicate that related therapeutic strategies may be particularly effective in individuals carrying ß-thalassemic gene defects.


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?


This article has been cited by other articles:


Home page
 BloodHome page
R. Mabaera, M. R. Greene, C. A. Richardson, S. J. Conine, C. D. Kozul, and C. H. Lowrey
Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin
Blood, January 1, 2008; 111(1): 411 - 420.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020