GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy.
- MeSH
- akutní erytroblastická leukemie genetika patologie MeSH
- akutní myeloidní leukemie genetika patologie MeSH
- buněčná diferenciace genetika MeSH
- DNA-(cytosin-5-)methyltransferasa genetika metabolismus MeSH
- genetická transkripce MeSH
- histony genetika MeSH
- lidé MeSH
- metylace DNA genetika MeSH
- promotorové oblasti (genetika) MeSH
- protoonkogenní proteiny biosyntéza genetika metabolismus MeSH
- regulace genové exprese u leukemie MeSH
- trans-aktivátory biosyntéza genetika metabolismus MeSH
- transkripční faktor GATA1 genetika metabolismus MeSH
- vazba proteinů MeSH
- zesilovače transkripce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
