ArticleHuman molecular genetics2010
Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Susceptibility of RUNX1 promoter rs2071029 polymorphism to adjuvant chemotherapy-induced neutropenia in CRC.Biomarkers in medicine · 2025Article
- Reflections and perspectives on epigenetically mediated biological control: compromises in cancer and skeletal pathology.Academia biology · 2025Article
- RUNX1 C-terminal mutations impair blood cell differentiation by perturbing specific enhancer-promoter networks.Blood advances · 2024Article
- RUNX1-Regulated Signaling Pathways in Ovarian Cancer.Biomedicines · 2023Review
- Loss ofInternational journal of molecular sciences · 2022Article
- Article
- RUNX regulated immune-associated genes predicts prognosis in breast cancer.Frontiers in genetics · 2022Article
- Runt related transcription factor-1 plays a central role in vessel co-option of colorectal cancer liver metastases.Communications biology · 2021Article
- Article
- RUNX family: Oncogenes or tumor suppressors (Review).Oncology reports · 2019Review
- RUNX1-dependent mechanisms in biological control and dysregulation in cancer.Journal of cellular physiology · 2019Review
- Identifying Nuclear Matrix-Attached DNA Across the Genome.Journal of cellular physiology · 2017Article
- RUNX1 truncation resulting from a cryptic and novel t(6;21)(q25;q22) chromosome translocation in acute myeloid leukemia: A case report.Oncology reports · 2016Article
- Mouse models for core binding factor leukemia.Leukemia · 2015Review
- The RUNX1 +24 enhancer and P1 promoter identify a unique subpopulation of hematopoietic progenitor cells derived from human pluripotent stem cells.Stem cells (Dayton, Ohio) · 2015Article
- Dynamic shifts in occupancy by TAL1 are guided by GATA factors and drive large-scale reprogramming of gene expression during hematopoiesis.Genome research · 2014Article
- Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients.Leukemia · 2014Article
- A germline point mutation in Runx1 uncouples its role in definitive hematopoiesis from differentiation.Experimental hematology · 2013Article
- Genomic promoter occupancy of runt-related transcription factor RUNX2 in Osteosarcoma cells identifies genes involved in cell adhesion and motility.The Journal of biological chemistry · 2012Article
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13 authors.
Funding
Abstract
Runx1 is a key hematopoietic transcription factor required for definitive hematopoiesis and is a frequent target of leukemia-related chromosomal translocations. The resulting fusion proteins, while retaining DNA binding activity, display loss of subnuclear targeting and associated transactivation functions encoded by the C-terminus of the protein. To define the precise contribution of the Runx1 C-terminus in development and leukemia, we created a knock-in mouse with a C-terminal truncation by introducing a single nucleic acid substitution in the native Runx1 locus. This mutation (Runx1(Q307X)) models genetic lesions observed in patients with leukemia and myeloproliferative disorders. The Runx1(Q307X) homozygous mouse exhibits embryonic lethality at E12.5 due to central nervous system hemorrhages and a complete lack of hematopoietic stem cell function. While able to bind DNA, Runx1(Q307X) is unable to activate target genes, resulting in deregulation of various hematopoietic markers. Thus, we demonstrate that the subnuclear targeting and transcriptional regulatory activities of the Runx1 C-terminus are critical for hematopoietic development. We propose that compromising the C-terminal functions of Runx1 is a common mechanism for the pathological consequences of a variety of somatic mutations and Runx1-related leukemic fusion proteins observed in human patients.
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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.