Journal Article

Activation of the β-like globin genes in transgenic mice is dependent on the presence of the β-locus control region

Patrick A. Navas, Qiliang Li, Kenneth R. Peterson, Richard A. Swank, Alex Rohde, Julianne Roy and George Stamatoyannopoulos

in Human Molecular Genetics

Volume 11, issue 8, pages 893-903
Published in print April 2002 | ISSN: 0964-6906
Published online April 2002 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/11.8.893
Activation of the β-like globin genes in transgenic mice is dependent on the presence of the β-locus control region

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The β-globin locus control region (LCR) is a powerful regulatory element required for high-level globin gene expression. We have generated transgenic mouse lines carrying a β-globin locus yeast artificial chromosome lacking the LCR to determine if the LCR is required for globin gene activation. β-Globin gene expression was analyzed by RNase protection, but no detectable levels of ε-, γ- and β-globin gene transcripts were produced at any stage of development. These findings suggest that the presence of the LCR is a minimum requirement for globin gene expression. Next, we tested whether the LCR is necessary to activate globin gene expression in a γ-globin promoter mutant that causes hereditary persistence of fetal hemoglobin (HPFH). β-YAC transgenic mice carrying the −117 HPFH mutation and a HS3 core deletion that specifically abolishes γ-globin gene expression during definitive erythropoiesis were produced to test whether the −117 Aγ promoter is activated in the absence of interaction with the LCR. In four transgenic mouse lines, γ-globin gene expression was absent in adult erythrocytes, suggesting that an interaction between the γ-globin gene promoter and the LCR is required for γ gene activation even when the promoter contains an HPFH mutation.

Journal Article.  8034 words.  Illustrated.

Subjects: Genetics and Genomics

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