ArticleNature communications2021
A unified model of human hemoglobin switching through single-cell genome editing.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Targeted protein degradation for fetal hemoglobin induction: a new paradigm in β-hemoglobinopathy therapy.Biomarker research · 2026Review
- Mechanisms of Globin Gene Regulation in Mammals.Annual review of genetics · 2025Review
- Characterization of diverse Cas9 orthologs for genome and epigenome editing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- FLT1 and other candidate fetal haemoglobin modifying loci in sickle cell disease in African ancestries.Nature communications · 2025Article
- Transcriptional regulators of fetal hemoglobin.Hematology, transfusion and cell therapy · 2024Review
- Enhancing terminal erythroid differentiation in human embryonic stem cells through TRIB3 overexpression.Heliyon · 2024Article
- Whole blood transcriptome analysis for age- and gender-specific gene expression profiling in Japanese individuals.Journal of biochemistry · 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
- RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.Developmental cell · 2023Article
- Erythroid lineage chromatin accessibility maps facilitate identification and validation of NFIX as a fetal hemoglobin repressor.Communications biology · 2023Article
- Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies.Molecular therapy. Nucleic acids · 2023Article
- Article
- Light-activated macromolecular phase separation modulates transcription by reconfiguring chromatin interactions.Science advances · 2023Article
- RNA Polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.medRxiv : the preprint server for health sciences · 2023Article
- Article
- Construction of a trio-based structural variation panel utilizing activated T lymphocytes and long-read sequencing technology.Communications biology · 2022Article
- LRF Promotes Indirectly Advantageous Chromatin Conformation viaInternational journal of molecular sciences · 2022Article
- Article
- Promoter competition in globin gene control.Blood · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Key mechanisms of fetal hemoglobin (HbF) regulation and switching have been elucidated through studies of human genetic variation, including mutations in the HBG1/2 promoters, deletions in the β-globin locus, and variation impacting BCL11A. While this has led to substantial insights, there has not been a unified understanding of how these distinct genetically-nominated elements, as well as other key transcription factors such as ZBTB7A, collectively interact to regulate HbF. A key limitation has been the inability to model specific genetic changes in primary isogenic human hematopoietic cells to uncover how each of these act individually and in aggregate. Here, we describe a single-cell genome editing functional assay that enables specific mutations to be recapitulated individually and in combination, providing insights into how multiple mutation-harboring functional elements collectively contribute to HbF expression. In conjunction with quantitative modeling and chromatin capture analyses, we illustrate how these genetic findings enable a comprehensive understanding of how distinct regulatory mechanisms can synergistically modulate HbF expression.
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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.