ArticleMolecular and cellular biology2005
Adult stage gamma-globin silencing is mediated by a promoter direct repeat element.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Epigenetic activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- Small molecule therapeutics to treat the β-globinopathies.Current opinion in hematology · 2020Review
- Prevention of Transcriptional γ-globin Gene Silencing by Inducing The Hereditary Persistence of Fetal Hemoglobin Point Mutation Using Chimeraplast-Mediated Gene Targeting.Cell journal · 2018Article
- Article
- An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference.Experimental hematology · 2015Review
- RN-1, a potent and selective lysine-specific demethylase 1 inhibitor, increases γ-globin expression, F reticulocytes, and F cells in a sickle cell disease mouse model.Experimental hematology · 2015Article
- 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
- 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
- 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
- Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities.Blood · 2011Review
- Human globin knock-in mice complete fetal-to-adult hemoglobin switching in postnatal development.Molecular and cellular biology · 2011Article
- Genome-wide binding of the orphan nuclear receptor TR4 suggests its general role in fundamental biological processes.BMC genomics · 2010Article
- Article
- SCF induces gamma-globin gene expression by regulating downstream transcription factor COUP-TFII.Blood · 2009Article
- Evidence for a bigenic chromatin subdomain in regulation of the fetal-to-adult hemoglobin switch.Molecular and cellular biology · 2009Article
- Silencing of Agamma-globin gene expression during adult definitive erythropoiesis mediated by GATA-1-FOG-1-Mi2 complex binding at the -566 GATA site.Molecular and cellular biology · 2008Article
- Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2 and TR4.The EMBO journal · 2007Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The human beta-like globin genes (5'-epsilon-Ggamma-Agamma-delta-beta-3') are temporally expressed in sequential order from the 5' to 3' end of the locus, but the nonadult epsilon- and gamma-globin genes are autonomously silenced in adult erythroid cells. Two cis elements have been proposed to regulate definitive erythroid gamma-globin repression: the DR (direct repeat) and CCTTG elements. Since these two elements partially overlap, and since a well-characterized HPFH point mutation maps to an overlapping nucleotide, it is not clear if both or only one of the two participate in gamma-globin silencing. To evaluate the contribution of these hypothetical silencers to gamma-globin regulation, we generated point mutations that individually disrupted either the single DR or all four CCTTG elements. These two were separately incorporated into human beta-globin yeast artificial chromosomes, which were then used to generate gamma-globin mutant transgenic mice. While DR element mutation led to a dramatic increase in Agamma-globin expression only during definitive erythropoiesis, the CCTTG mutation did not affect adult stage transcription. These results demonstrate that the DR sequence element autonomously mediates definitive stage-specific gamma-globin gene silencing.
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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.