ArticleCell chemical biology2022
Temporal resolution of gene derepression and proteome changes upon PROTAC-mediated degradation of BCL11A protein in erythroid cells.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Targeted protein degradation for fetal hemoglobin induction: a new paradigm in β-hemoglobinopathy therapy.Biomarker research · 2026Review
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- Regulation of BCL11A DNA binding and expression in human erythrocyte precursor HUDEP-2 cells.bioRxiv : the preprint server for biology · 2026Article
- Scaffolding-dependent CASP1 constrains excessive cell-intrinsic inflammatory signaling in leukemia.Cell chemical biology · 2026Article
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 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
- BCL11A-deficient human erythropoiesis is impaired in vitro and after xenotransplantation into mice.Blood advances · 2025Article
- Solution structure of the Z0 domain from transcription repressor BCL11A sheds light on the sequence properties of protein-binding zinc fingers.Protein science : a publication of the Protein Society · 2025Article
- Redirecting E3 ubiquitin ligases for targeted protein degradation with heterologous recognition domains.The Journal of biological chemistry · 2025Article
- Targeted degradation of oncogenic KRASG12V triggers antitumor immunity in lung cancer models.The Journal of clinical investigation · 2024Article
- Structural insights into the DNA-binding mechanism of BCL11A: The integral role of ZnF6.Structure (London, England : 1993) · 2024Article
- A tetramer of BCL11A is required for stable protein production and fetal hemoglobin silencing.Science (New York, N.Y.) · 2024Article
- The glucocorticoid receptor elicited proliferative response in human erythropoiesis is BCL11A-dependent.Stem cells (Dayton, Ohio) · 2024Article
- PROTAC-mediated vimentin degradation promotes terminal erythroid differentiation of pluripotent stem cells.Stem cell research & therapy · 2024Article
- Base editing of key residues in the BCL11A-XL-specific zinc finger domains derepresses fetal globin expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Chemical-genetics refines transcription factor regulatory circuits.Trends in cancer · 2024Review
- Transcriptional Repressor BCL11A in Erythroid Cells.Advances in experimental medicine and biology · 2024Review
- Role of PDGFRANature communications · 2023Article
- Emerging insights into enhancer biology and function.Transcription · 2023Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Reactivation of fetal hemoglobin expression by the downregulation of BCL11A is a promising treatment for β-hemoglobinopathies. A detailed understanding of BCL11A-mediated repression of γ-globin gene (HBG1/2) transcription is lacking, as studies to date used perturbations by shRNA or CRISPR-Cas9 gene editing. We leveraged the dTAG PROTAC degradation platform to acutely deplete BCL11A protein in erythroid cells and examined consequences by nascent transcriptomics, proteomics, chromatin accessibility, and histone profiling. Among 31 genes repressed by BCL11A, HBG1/2 and HBZ show the most abundant and progressive changes in transcription and chromatin accessibility upon BCL11A loss. Transcriptional changes at HBG1/2 were detected in <2 h. Robust HBG1/2 reactivation upon acute BCL11A depletion occurred without the loss of promoter 5-methylcytosine (5mC). Using targeted protein degradation, we establish a hierarchy of gene reactivation at BCL11A targets, in which nascent transcription is followed by increased chromatin accessibility, and both are uncoupled from promoter DNA methylation at the HBG1/2 loci.
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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 Socratic graph.