ArticleNature2015
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 547 papers.
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Who cites it
547 citing papers in PubMed, 897 citations in OpenAlex.
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- Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context.Cell · 2026Article
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- Towards efficient perturbation for the noncoding genome.Nature communications · 2026Article
- Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026Review
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.Genome biology · 2026Article
- Massively parallel characterization and predictive modelling of neuronal regulatory variation.bioRxiv : the preprint server for biology · 2026Article
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- The Journey of Gene Therapy in Sickle Cell Disease: How Molecular Advances Meet Clinical Care.Cells · 2026Review
- AI platform for CRISPR functional mapping and function-based drug design.bioRxiv : the preprint server for biology · 2026Article
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- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- CRISPR-Cas9-Mediated Gene Editing in Hematological Disorders: Advancing Translational and Clinical Applications.Cureus · 2026Review
487 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements.
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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.