Key regulators control distinct transcriptional programmes in blood progenitor and mast cells.
Title | Key regulators control distinct transcriptional programmes in blood progenitor and mast cells. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Calero-Nieto, F. J., Ng F. S., Wilson N. K., Hannah R., Moignard V., Leal-Cervantes A. I., Jimenez-Madrid I., Diamanti E., Wernisch L., & Göttgens B. |
Journal | EMBO J |
Volume | 33 |
Issue | 11 |
Pagination | 1212-26 |
Date Published | 2014 Jun 2 |
ISSN | 1460-2075 |
Keywords | Animals, Cell Line, Gene Expression Profiling, Gene Expression Regulation, Genes, Reporter, Genome-Wide Association Study, Hematopoiesis, Mast Cells, Mice, Models, Statistical, Nucleotide Motifs, Oligonucleotide Array Sequence Analysis, Sequence Analysis, DNA, Sequence Analysis, RNA, Stem Cells, Transcription Factors, Transcription, Genetic |
Abstract | 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. |
DOI | 10.1002/embj.201386825 |
Alternate Journal | EMBO J. |
PubMed ID | 24760698 |
PubMed Central ID | PMC4168288 |
Grant List | BBS/B/1454X / / Biotechnology and Biological Sciences Research Council / United Kingdom G0900951 / / Medical Research Council / United Kingdom MC_U105260799 / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom |