Sequences in the A γ–δ intergenic region are not required for stage-specific regulation of the human β-globin gene locus
| Autor: | Linda Flebbe-Rehwaldt, Chin Lin, Zemin Zhang, Karin M.L. Gaensler, Karin Hardt, Suya Yang |
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| Rok vydání: | 2003 |
| Předmět: |
Genetics
Yeast artificial chromosome Multidisciplinary Gene Expression Regulation Developmental Mice Transgenic Locus (genetics) Biological Sciences Biology Molecular biology Globins Mice Intergenic region Regulatory sequence Genes Regulator Mutation Gene cluster Animals Humans Gene family Gene Silencing Globin Chromosomes Artificial Yeast Gene Sequence Deletion |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:3374-3379 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0634132100 |
| Popis: | The human β-globin locus has been extensively studied as a model of tissue and developmental stage-specific gene expression. Structural mapping of naturally occurring mutations, including transfection and transgenic studies, and the recent finding of intergenic transcripts have suggested that there are cis-acting sequence elements in the A γ–δ intergenic region involved in regulating γ- and β-globin gene expression. To determine whether previously identified sequences in the A γ–δ intergenic region are required for appropriate developmental expression of the human β-globin gene cluster, transgenic mice were generated by transfer of yeast artificial chromosomes containing the entire human β-globin locus. Three different deletions of the A γ–δ intergenic region were introduced, including ( i ) deletion of the 750-bp A γ 3′ regulatory element ( A γe), ( ii ) deletion of 3.2 kb upstream of the δ-globin gene encompassing pyrimidine-rich sequences and the recently described intergenic transcript initiation site, and ( iii ) deletion of a 12.5-kb fragment encompassing most of the A γ–δ globin intergenic region. Analysis of multiple transgenic lines carrying these deletion constructs demonstrated that the normal stage-specific sequential expression of the ɛ-, γ-, and β-globin genes was preserved, despite deletion of these putative regulatory sequences. These studies suggest that regulatory sequences required for activation and silencing of the human β-globin gene family during ontogeny reside proximally to the genes and immediately 5′ to the human γ- and β-globin genes. |
| Databáze: | OpenAIRE |
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