ArticleThe Journal of biological chemistry2010
Developmental silencing of human zeta-globin gene expression is mediated by the transcriptional repressor RREB1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- A novel interaction between RNA mBiochemical and biophysical research communications · 2024Article
- Dictys: dynamic gene regulatory network dissects developmental continuum with single-cell multiomics.Nature methods · 2023Article
- Unannotated single nucleotide polymorphisms in the TATA box of erythropoiesis genes show in vitro positive involvements in cognitive and mental disorders.BMC medical genetics · 2020Article
- Transcription Factor RREB1: from Target Genes towards Biological Functions.International journal of biological sciences · 2020Review
- RAS-Responsive Element-Binding Protein 1 Blocks the Granulocytic Differentiation of Myeloid Leukemia Cells.Oncology research · 2019Article
- A new computational method to predict transcriptional activity of a DNA sequence from diverse datasets of massively parallel reporter assays.Nucleic acids research · 2017Article
- Functional footprinting of regulatory DNA.Nature methods · 2015Article
- Pharmacological Induction of Human Fetal Globin Gene in Hydroxyurea-Resistant Primary Adult Erythroid Cells.Molecular and cellular biology · 2015Article
- CtBP and associated LSD1 are required for transcriptional activation by NeuroD1 in gastrointestinal endocrine cells.Molecular and cellular biology · 2014Article
- Mammalian-wide interspersed repeat (MIR)-derived enhancers and the regulation of human gene expression.Mobile DNA · 2014Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian embryonic zeta-globin genes, including that of humans, are expressed at the early embryonic stage and then switched off during erythroid development. This autonomous silencing of the zeta-globin gene transcription is probably regulated by the cooperative work of various protein-DNA and protein-protein complexes formed at the zeta-globin promoter and its upstream enhancer (HS-40). We present data here indicating that a protein-binding motif, ZF2, contributes to the repression of the HS-40-regulated human zeta-promoter activity in erythroid cell lines and in transgenic mice. Combined site-directed mutagenesis and EMSA suggest that repression of the human zeta-globin promoter is mediated through binding of the zinc finger factor RREB1 to ZF2. This model is further supported by the observation that human zeta-globin gene transcription is elevated in the human erythroid K562 cell line or the primary erythroid culture upon RNA interference (RNAi)(2) knockdown of RREB1 expression. These data together suggest that RREB1 is a putative repressor for the silencing of the mammalian zeta-globin genes during erythroid development. Because zeta-globin is a powerful inhibitor of HbS polymerization, our experiments have provided a foundation for therapeutic up-regulation of zeta-globin gene expression in patients with severe hemoglobinopathies.
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