ArticleProceedings of the National Academy of Sciences of the United States of America2016
Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Pooled it
- Congenital dyserythropoietic anemia type I: First report from the Congenital Dyserythropoietic Anemia Registry of North America (CDAR).Blood cells, molecules & diseases · 2021Trial
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- Distinguishing causal from tagging enhancers using single-cell multiome data.medRxiv : the preprint server for health sciences · 2026Article
- Advances in the characterization of in vitro-generated red blood cells: from biophysical properties to functional applications.Stem cell research & therapy · 2025Review
- Linking regulatory variants to target genes by integrating single-cell multiome methods and genomic distance.Nature genetics · 2025Article
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- ChromActivity: integrative epigenomic and functional characterization assay based annotation of regulatory activity across diverse human cell types.Genome biology · 2025Article
- Functional dissection of complex and molecular trait variants at single nucleotide resolution.bioRxiv : the preprint server for biology · 2024Article
- Characterizing genetic variation in the regulation of the ER stress response through computational and cis-eQTL analyses.G3 (Bethesda, Md.) · 2023Article
- Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions.Nature genetics · 2023Article
- Computational Assessment of the Expression-modulating Potential for Non-coding Variants.Genomics, proteomics & bioinformatics · 2023Article
- Review
- A comparison of experimental assays and analytical methods for genome-wide identification of active enhancers.Nature biotechnology · 2022Article
- Article
- Identification of Germline Non-coding Deletions in XIAP Gene Causing XIAP Deficiency Reveals a Key Promoter Sequence.Journal of clinical immunology · 2022Article
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- Loop competition and extrusion model predicts CTCF interaction specificity.Nature communications · 2021Article
- Discovering How Heme Controls Genome Function Through Heme-omics.Cell reports · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptionalcis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonical GATA1 binding motif completely abrogated binding of the cofactor TAL1, which binds to a separate motif. Having verified the functionality of these three GATA1 motifs, we demonstrate strong evolutionary conservation of GATA1 motifs in regulatory elements proximal to other genes implicated in erythroid disorders, and show that targeted disruption of such elements results in altered gene expression. By modeling transcription factor binding patterns, we show that multiple transcription factors are associated with erythroid gene expression, and have created predictive maps modeling putative disruptions of their binding sites at key regulatory elements. Our study provides insight into GATA1 transcriptional activity and may prove a useful resource for investigating the pathogenicity of noncoding variants in human erythroid disorders.
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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.