Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo.

Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Research Abstract Details 

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Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Abstract Text:

Zhenning He,J Eric Russell,

Functional studies of embryonic epsilon-globin indicate that individuals with beta 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 beta thalassemia, suggesting that epsilon- and beta-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 beta-thalassemic gene defects.

Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Publishing Authors By Initials

Z He,JE Russell,

For similar hemic and lymphatic diseases: hematologic diseases: anemia: anemia, hemolytic: anemia, hemolytic, congenital: thalassemia: beta-thalassemia research abstracts see: hemic and lymphatic diseases: hematologic diseases: anemia: anemia, hemolytic: anemia, hemolytic, congenital: thalassemia: beta-thalassemia research

PUBMED ID PMID:

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Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Blood

VOLUME: 109

Page Numbers: 795-801

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 26

MONTH: 09

YEAR: 2006

Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Keywords Mesh Terms:

KEYWORDS: beta-Thalassemia

MESH TERMS: genetics

Chemical & Substance for Abstract: Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Information

Substance Name: Globins

Registry Number: 9004-22-2

Grant and Affiliation Information for Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo.

AFFILIATION: Department of Medicine, University of Pennsylvania School of Medicine, and The Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-U54-070596

ACRONYM: HL

MEDLINETA: Blood

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