ArticlePLoS genetics2012
Mi2β is required for γ-globin gene silencing: temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in β-YAC transgenic mice.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis.Nature genetics · 2019Article
- Oxidative Stress in β-Thalassemia.Molecular diagnosis & therapy · 2019Review
- Engineering Globin Gene Expression.Molecular therapy. Methods & clinical development · 2019Review
- Article
- Mouse Models of Erythropoiesis and Associated Diseases.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Modulating the expression of Chtop, a versatile regulator of gene-specific transcription and mRNA export.RNA biology · 2018Review
- Gene Therapy for β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Article
- Pathophysiology and treatment of patients with beta-thalassemia - an update.F1000Research · 2017Review
- Hemoglobin genetics: recent contributions of GWAS and gene editing.Human molecular genetics · 2016Review
- Gamma reactivation using the spongy effect of KLF1-binding site sequence: an approach in gene therapy for beta-thalassemia.Iranian journal of basic medical sciences · 2016Article
- O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter.The Journal of biological chemistry · 2016Article
- Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- Epigenetic regulation of fetal globin gene expression in adult erythroid cells.Translational research : the journal of laboratory and clinical medicine · 2015Review
- The nucleosome remodeling and deacetylase complex in development and disease.Translational research : the journal of laboratory and clinical medicine · 2015Review
- Fetal globin gene repressors as drug targets for molecular therapies to treat the β-globinopathies.Molecular and cellular biology · 2014Review
- Extensively self-renewing erythroblasts derived from transgenic β-yac mice is a novel model system for studying globin switching and erythroid maturation.Experimental hematology · 2014Article
- Transcriptional mechanisms underlying hemoglobin synthesis.Cold Spring Harbor perspectives in medicine · 2013Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Activation of γ-globin gene expression in adults is known to be therapeutic for sickle cell disease. Thus, it follows that the converse, alleviation of repression, would be equally effective, since the net result would be the same: an increase in fetal hemoglobin. A GATA-1-FOG-1-Mi2 repressor complex was recently demonstrated to be recruited to the -566 GATA motif of the (A)γ-globin gene. We show that Mi2β is essential for γ-globin gene silencing using Mi2β conditional knockout β-YAC transgenic mice. In addition, increased expression of (A)γ-globin was detected in adult blood from β-YAC transgenic mice containing a T>G HPFH point mutation at the -566 GATA silencer site. ChIP experiments demonstrated that GATA-1 is recruited to this silencer at day E16, followed by recruitment of FOG-1 and Mi2 at day E17 in wild-type β-YAC transgenic mice. Recruitment of the GATA-1-mediated repressor complex was disrupted by the -566 HPFH mutation at developmental stages when it normally binds. Our data suggest that a temporal repression mechanism is operative in the silencing of γ-globin gene expression and that either a trans-acting Mi2β knockout deletion mutation or the cis-acting -566 (A)γ-globin HPFH point mutation disrupts establishment of repression, resulting in continued γ-globin gene transcription during adult definitive erythropoiesis.
Indexed as
Identifiers
What OpenQuestion holds
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.