ArticleHaematologica2012
The role of WDR5 in silencing human fetal globin gene expression.
Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- MAZ regulates fetal hemoglobin repression by activating MYB transcription.Scientific reports · 2025Article
- Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.Epigenetics · 2025Review
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Inhibitor of Growth Proteins: Epigenetic Regulators Shaping Neurobiology.Biomolecules · 2025Review
- PRMT5: a putative oncogene and therapeutic target in prostate cancer.Cancer gene therapy · 2022Review
- Transcriptional silencing of fetal hemoglobin expression by NonO.Nucleic acids research · 2021Article
- WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1α accumulation in Myc-dependent and independent pathways.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Targeting sickle cell disease root-cause pathophysiology with small molecules.Haematologica · 2019Review
- Fetal Hemoglobin Induction by Epigenetic Drugs.Seminars in hematology · 2018Review
- Heterochromatin Protein 1γ Is a Novel Epigenetic Repressor of Human Embryonic ϵ-Globin Gene Expression.The Journal of biological chemistry · 2017Article
- Neuronal necrosis is regulated by a conserved chromatin-modifying cascade.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistone H3 lysine 4 (K4) methylation has been linked with transcriptional activity in mammalian cells. The WD40-repeat protein, WDR5, is an essential component of the MLL complex that induces histone H3 K4 methylation, but the role of WDR5 in human globin gene regulation has not yet been established. DESIGN AND
methodsTo study the role of WDR5 in human globin gene regulation, we performed knockdown experiments in both K562 cells and primary human bone marrow erythroid progenitor cells (BMC). The effects of WDR5 knockdown on γ-globin gene expression were determined. Biochemical approaches were also employed to investigate WDR5 interaction molecules. Chromosomal marks in the globin locus were analyzed by ChIP.
resultsWe found that WDR5 interacted with protein arginine methyltransferase 5 (PRMT5), a known repressor of γ-globin gene expression, and was essential for generating tri-methylated H3K4 (H3K4me3) at the γ-globin promoter in K562 cells. Enforced expression of WDR5 in K562 cells reduced γ-globin gene expression, whereas knockdown of WDR5 increased γ-globin gene expression in both K562 cells and primary human bone marrow erythroid progenitor cells. Consistent with this, both histone H3 and H4 acetylation at the γ-globin promoter were increased, while histone H4R3 and H3K9 methylation were decreased, in WDR5 knockdown cells compared to controls. We found that WDR5 interacted with HDAC1 and a PHD domaincontaining protein, ING2 (inhibitor of growth), an H3K4me3 mark reader, to enhance γ-globin gene transcriptional repression. In human BMC, levels of WDR5 were highly enriched on the γ-promoter relative to levels on other globin promoters and compared to the γ-promoter in cord blood erythroid progenitors, suggesting that WDR5 is important in the developmental globin gene expression program.
conclusionsOur data are consistent with a model in which WDR5 binds the γ-globin promoter in a PRMT5-dependent manner; H3K4me3 induced at the γ-globin promoter by WDR5 may result in the recruitment of the ING2-associated HDAC1 component and consequent silencing of γ-globin gene expression.
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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.