ArticleGenes & development2000
Context-dependent EKLF responsiveness defines the developmental specificity of the human epsilon-globin gene in erythroid cells of YAC transgenic mice.
Article in Genes & development, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 75 citations in OpenAlex.
- Five nucleotides found in RCTG motifs are essential for post-fertilization methylation imprinting of the H19 ICR in YAC transgenic mice.Nucleic acids research · 2023Article
- Epigenetic activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- Small molecule therapeutics to treat the β-globinopathies.Current opinion in hematology · 2020Review
- Recapitulation of gametic DNA methylation and its post-fertilization maintenance with reassembled DNA elements at the mouse Igf2/H19 locus.Epigenetics & chromatin · 2020Article
- Synthetic DNA fragments bearing ICR cis elements become differentially methylated and recapitulate genomic imprinting in transgenic mice.Epigenetics & chromatin · 2018Article
- ε-globin expression is regulated by SUV4-20h1.Haematologica · 2016Article
- Article
- Fetal globin gene repressors as drug targets for molecular therapies to treat the β-globinopathies.Molecular and cellular biology · 2014Review
- PGC-1 coactivator activity is required for murine erythropoiesis.Molecular and cellular biology · 2014Article
- Article
- Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing.Molecular and cellular biology · 2013Article
- The H19 imprinting control region mediates preimplantation imprinted methylation of nearby sequences in yeast artificial chromosome transgenic mice.Molecular and cellular biology · 2013Article
- Multiple roles of COUP-TFII in cancer initiation and progression.Journal of molecular endocrinology · 2012Review
- JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny.Journal of translational medicine · 2012Article
- Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator.Anemia · 2012Article
- Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Review
- Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells.Molecular and cellular biology · 2011Article
- MBD2 contributes to developmental silencing of the human ε-globin gene.Blood cells, molecules & diseases · 2011Article
- The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
We explored the mechanism of definitive-stage epsilon-globin transcriptional inactivity within a human beta-globin YAC expressed in transgenic mice. We focused on the globin CAC and CAAT promoter motifs, as previous laboratory and clinical studies indicated a pivotal role for these elements in globin gene activation. A high-affinity CAC-binding site for the erythroid krüppel-like factor (EKLF) was placed in the epsilon-globin promoter at a position corresponding to that in the adult beta-globin promoter, thereby simultaneously ablating a direct repeat (DR) element. This mutation led to EKLF-independent epsilon-globin transcription during definitive erythropoiesis. A second 4-bp substitution in the epsilon-globin CAAT sequence, which simultaneously disrupts a second DR element, further enhanced ectopic definitive erythroid activation of epsilon-globin transcription, which surprisingly became EKLF dependent. We finally examined factors in nuclear extracts prepared from embryonic or adult erythroid cells that bound these elements in vitro, and we identified a novel DR-binding protein (DRED) whose properties are consistent with those expected for a definitive-stage epsilon-globin repressor. We conclude that the suppression of epsilon-globin transcription during definitive erythropoiesis is mediated by the binding of a repressor that prevents EKLF from activating the epsilon-globin gene.
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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.