Despite major advances in the generation of genome-wide binding maps, the mechanisms by which transcription factors (TFs) regulate cell type identity have remained largely obscure. Through comparative analysis of 10 key haematopoietic TFs in both mast cells and blood progenitors, we demonstrate that the largely cell type-specific binding profiles are not opportunistic, but instead contribute to cell type-specific transcriptional control, because (i) mathematical modelling of differential binding of shared TFs can explain differential gene expression, (ii) consensus binding sites are important for cell type-specific binding and (iii) knock-down of blood stem cell regulators in mast cells reveals mast cell-specific genes as direct targets. Finally, we show that the known mast cell regulators Mitf and c-fos likely contribute to the global reorganisation of TF binding profiles. Taken together therefore, our study elucidates how key regulatory TFs contribute to transcriptional programmes in several distinct mammalian cell types.
Comparative profiling of ten key haematopoietic transcription factors in blood progenitors versus mast cells demonstrates tissue-specific binding profiles that functionally determine cellular identify.
- Genome-wide binding profiles for 10 TFs in blood progenitors and mast cells
- Differential binding of shared TFs is predictive of differential gene expression.
- Cell type-specific TFs may reorganise global binding profiles of shared TFs.
- Cell type-specific binding of shared TFs is not predominantly opportunistic.