A bistable genetic switch which does not require high co-operativity at the promoter: a two-timescale model for the PU.1-GATA-1 interaction.
The transcription factors PU.1 and GATA-1 antagonize each other in common myeloid progenitors and their relative abundance is thought to decide whether the cell follows the erythrocyte/megakaryocyte lineage or the granulocyte/macrophage lineage. We propose a kinetic model for the PU.1-GATA-1 interaction, analyse its phase space and interpret the results of our analysis. The conclusions have broader implications for the modelling of cell-fate selection.
Bokes
Pavol
P
Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham NG7 2RD, UK. pmxpb@nottingham.ac.uk
King
John R
JR
Loose
Matthew
M
D000465:Algorithms; D000818:Animals; D004247:DNA / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005812:Genes, Switch / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008957:Models, Genetic; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D049490:Systems Biology; D015534:Trans-Activators / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D004247:DNA; D050982:GATA1 Transcription Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1