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Distinct negative regulation of the human embryonic globin genes ζ and

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The human embryonic globin genes ζ and are expressed when erythropoies is is initiated at about the third week of development but are subsequently repressed as expression of the fetal globins, and , begins. We have examined the promoter region of the human ζ-globin and -globin genes in order to identify regulatory sequences that may be involved in this process. Stable transfection of the human erythroid cell line K562 with either a truncated form of the ζ-globin gene, containing 112 base pairs (bp) of 5-flanking sequences, or a larger ζ-globin construct, containing several hundred bp o f 5-flanking sequence, revealed that the ζ-globin gene is subject to negative regulation by its 5-flanking region. We have defined the sequences responsible for this negative regulation to a 22 bp region immediately upstream of the proximal promoter sequence of the ζ-globin gene. A 22 bp oligonucleotide including this negative element was found to inhibit both the ζ-globin and HSV TK promoters. We have also analyzed the promoter of the human -globin gene, since it is coordinately expressed with ζ-globin. We show that it is likewise subject to negative regulation, though in this case from a distal silencer element. Gel retardation and methylation interference assays have provided evidence of a factor which binds specifically to the -globin silencer. However, no obvious sequence homology exists between the ζ and negative elements, and at least some of the factors that recognize these elements are distinct. We postulate that the negative transcriptional control elements in the human embryonic globin gene promoters contribute to the observed reduction in and -globin gene expression that occurs during development.
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Document Type: Research Article

Publication date: January 1, 1993

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  • Gene Expression The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.

    From Volume 16, Gene Expression The Journal of Liver Research is Open Access under the terms of the Creative Commons CC BY-NC-ND license.

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