E-GEOD-55244 - Genome-scale analysis in blood progenitor and mast cells reveals how lineage-affiliated transcription factors control distinct regulatory programs [Beadchip Experiments #2]
Released on 24 April 2014, last updated on 13 May 2014
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 (1) mathematical modelling of differential binding of shared TFs can explain differential gene expression, (2) cell-type specific binding is largely mediated through consensus binding sites, and (3) knock-down of blood stem cell regulators Gata2 and Erg 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. Total RNA from primary mast cells transfected with retroviral shRNA vectors were compared to negative controls (shRNA against luciferase).
transcription profiling by array
Felicia Ng <firstname.lastname@example.org>, Ana I Leal-Cervantes, Berthold Gottgens, Evangelia Diamanti, Felicia S Ng, Fernando J Calero-Nieto, Isabel Jimenez-Madrid, Lorenz Wernisch, Nicola K Wilson, Rebecca Hannah, Victoria Moignard