ArticleThe EMBO journal1999
A 3'-flanking NF-kappaB site mediates developmental silencing of the human zeta-globin gene.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 23 citations in OpenAlex.
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Article
- Hydroxyurea-inducible SAR1 gene acts through the Giα/JNK/Jun pathway to regulate γ-globin expression.Blood · 2014Article
- Structural determinants of human ζ-globin mRNA stability.Journal of hematology & oncology · 2014Article
- NF-kappaB regulation of YY1 inhibits skeletal myogenesis through transcriptional silencing of myofibrillar genes.Molecular and cellular biology · 2007Article
- The control of expression of the alpha-globin gene cluster.International journal of hematology · 2002Review
- Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Loading of DNA-binding factors to an erythroid enhancer.Molecular and cellular biology · 2000Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The central developmental event in the human (h)alpha-globin gene cluster is selective silencing of the zeta-globin gene as erythropoiesis shifts from primitive erythroblasts in the embryonic yolk sac to definitive erythroblasts in the fetal liver. Previous studies have demonstrated that full developmental silencing of the hzeta-globin gene in transgenic mice requires the proximal 2.1 kb of its 3'-flanking region. In the current report, we localize this silencing activity to a 108 bp segment located 1.2 kb 3' to the zeta-globin gene. Protein(s) in nuclear extracts from cell lines representing the fetal/adult erythroid stage bind specifically to an NF-kappaB motif located at this site. In contrast, this binding activity is lacking in the nuclear extract of an embryonic-stage erythroid line expressing zeta-globin. This complex is quantitatively recognized by antisera to the NF-kappaB p50 and to a lesser extent to p65 subunits. A two-base substitution that disrupts NF-kappaB site protein binding in vitro also results in the loss of the developmental silencing activity in vivo. The data suggest that NF-kappaB complex formation is a crucial component of hzeta-globin gene silencing. This finding expands the roles of this widely distributed transcriptional complex to include negative regulation in mammalian development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.