ArticleNature genetics2019
Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis.
Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 108 citations in OpenAlex.
- Direct and indirect regulation of fetal globin transcript by the RNA-binding protein IGF2BP1.Blood · 2026Article
- Motif-Cluster: Motif driven prioritization of transcription factor binding clusters.PLoS computational biology · 2026Article
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- AI platform for CRISPR functional mapping and function-based drug design.bioRxiv : the preprint server for biology · 2026Article
- Dissecting polycomb complexes for enhanced fetal hemoglobin production.bioRxiv : the preprint server for biology · 2026Article
- Directing stem cell differentiation by chromatin state approximation.Nucleic acids research · 2026Article
- Comprehensive Review of Genetic and Epigenetic Regulation of Fetal Hemoglobin in β-Hemoglobinopathies: From Molecular Mechanisms to Clinical Applications.Mediterranean journal of hematology and infectious diseases · 2026Review
- Review
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Direct and indirect regulation of fetal globin transcript by RNA-binding protein IGF2BP1.bioRxiv : the preprint server for biology · 2025Article
- Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis.Experimental hematology · 2025Review
- Beyond transfusions and transplants: genomic innovations rewriting the narrative of thalassemia.Annals of hematology · 2025Review
- Removal of promoter CpG methylation by epigenome editing reverses HBG silencing.Nature communications · 2025Article
- Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.Nucleic acids research · 2025Article
- Article
- The role of multivalency in the association of the eight twenty-one protein 2 (ETO2) with the nucleosome remodeling and deacetylase (NuRD) complex.Nucleic acids research · 2025Article
- In vivo deletion of a GWAS-identified Myb distal enhancer acts on Myb expression, globin switching, and clinical erythroid parameters in β-thalassemia.Scientific reports · 2025Article
- Review
- A tetramer of BCL11A is required for stable protein production and fetal hemoglobin silencing.Science (New York, N.Y.) · 2024Article
- Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
Abstract
Developmental silencing of fetal globins serves as both a paradigm of spatiotemporal gene regulation and an opportunity for therapeutic intervention of β-hemoglobinopathy. The nucleosome remodeling and deacetylase (NuRD) chromatin complex participates in γ-globin repression. We used pooled CRISPR screening to disrupt NuRD protein coding sequences comprehensively in human adult erythroid precursors. Essential for fetal hemoglobin (HbF) control is a non-redundant subcomplex of NuRD protein family paralogs, whose composition we corroborated by affinity chromatography and proximity labeling mass spectrometry proteomics. Mapping top functional guide RNAs identified key protein interfaces where in-frame alleles resulted in loss-of-function due to destabilization or altered function of subunits. We ascertained mutations of CHD4 that dissociate its requirement for cell fitness from HbF repression in both primary human erythroid precursors and transgenic mice. Finally we demonstrated that sequestering CHD4 from NuRD phenocopied these mutations. These results indicate a generalizable approach to discover protein complex features amenable to rational biochemical targeting.
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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.