ArticlePLoS genetics2010
A single cis element maintains repression of the key developmental regulator Gata2.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 52 citations in OpenAlex.
- GATA Transcription Factors: A Cross-Road for Erythropoiesis, Neurodevelopment, and Synucleinopathies.Developmental neurobiology · 2025Review
- Article
- TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression.Nature communications · 2023Article
- Conditionally pathogenic genetic variants of a hematopoietic disease-suppressing enhancer.Science advances · 2021Article
- Essential role for Gata2 in modulating lineage output from hematopoietic stem cells in zebrafish.Blood advances · 2021Article
- Human GATA2 mutations and hematologic disease: how many paths to pathogenesis?Blood advances · 2020Review
- GATA2 +9.5 enhancer: from principles of hematopoiesis to genetic diagnosis in precision medicine.Current opinion in hematology · 2020Review
- Blood disease-causing and -suppressing transcriptional enhancers: general principles andBlood advances · 2019Review
- lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.Cell reports · 2019Article
- CpG traffic lights are markers of regulatory regions in human genome.BMC genomics · 2019Article
- Transcription factor mutations as a cause of familial myeloid neoplasms.The Journal of clinical investigation · 2019Review
- Integrating Enhancer Mechanisms to Establish a Hierarchical Blood Development Program.Cell reports · 2017Article
- GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia.Developmental cell · 2017Article
- The GATA factor revolution in hematology.Blood · 2017Review
- GATA2 deficiency and related myeloid neoplasms.Seminars in hematology · 2017Article
- Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis.Developmental cell · 2016Article
- GATA1 Activity Governed by Configurations ofFrontiers in oncology · 2016Review
- The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.Current topics in developmental biology · 2016Review
- Cis-regulatory mechanisms governing stem and progenitor cell transitions.Science advances · 2015Article
- Histone methyltransferase Setd8 represses Gata2 expression and regulates erythroid maturation.Molecular and cellular biology · 2015Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In development, lineage-restricted transcription factors simultaneously promote differentiation while repressing alternative fates. Molecular dissection of this process has been challenging as transcription factor loci are regulated by many trans-acting factors functioning through dispersed cis elements. It is not understood whether these elements function collectively to confer transcriptional regulation, or individually to control specific aspects of activation or repression, such as initiation versus maintenance. Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2, which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. We engineered mice lacking a single cis element -1.8 kb upstream of the Gata2 transcriptional start site. Although Gata2 is normally repressed in late-stage erythroblasts, the -1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. Our findings demonstrate that the -1.8 kb site selectively maintains repression, confers a specific histone modification pattern and expels RNA Polymerase II from the locus. These studies reveal how an individual cis element establishes a normal developmental program via regulating specific steps in the mechanism by which a critical transcription factor is repressed.
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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.