DNMT1 is the maintenance DNA methyltransferase shown to be essential for embryonic development and cellular growth and differentiation in many somatic tissues in mammals. Increasing evidence has also suggested a role for DNMT1 in repressing gene expression through interactions with specific transcription factors. Previously, we identified DNMT1 as an interacting partner of the TR2/TR4 nuclear receptor heterodimer in erythroid cells, implicated in the developmental silencing of fetal β-type globin genes in the adult stage of human erythropoiesis. Here, we extended this work by using a biotinylation tagging approach to characterize DNMT1 protein complexes in mouse erythroleukemic cells. We identified novel DNMT1 interactions with several hematopoietic transcription factors with essential roles in erythroid differentiation, including GATA1, GFI-1b and FOG-1. We provide evidence for DNMT1 forming distinct protein subcomplexes with specific transcription factors and propose the existence of a "core" DNMT1 complex with the transcription factors ZBP-89 and ZNF143, which is also present in non-hematopoietic cells. Furthermore, we identified the short (17a.a.) PCNA Binding Domain (PBD) located near the N-terminus of DNMT1 as being necessary for mediating interactions with the transcription factors described herein. Lastly, we provide evidence for DNMT1 serving as a co-repressor of ZBP-89 and GATA1 acting through upstream regulatory elements of the PU.1 and GATA1 gene loci.
- MeSH
- buněčná diferenciace genetika MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- DNA-(cytosin-5-)methyltransferasa genetika metabolismus MeSH
- DNA-(cytosin-5)-methyltransferasa 1 MeSH
- erytroidní buňky chemie metabolismus MeSH
- jaderné proteiny genetika metabolismus MeSH
- lidé MeSH
- metylace DNA genetika MeSH
- multiproteinové komplexy genetika metabolismus MeSH
- myši MeSH
- protoonkogenní proteiny genetika metabolismus MeSH
- regulace genové exprese genetika MeSH
- represorové proteiny genetika metabolismus MeSH
- trans-aktivátory genetika metabolismus MeSH
- transkripční faktor GATA1 genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH