Cooperative binding of AP-1 and TEAD4 modulates the balance between vascular smooth muscle and hemogenic cell fate

The transmission of extracellular signals into the nucleus involves inducible transcription factors, but how different signalling pathways act in a cell type-specific fashion is poorly understood. Here, we studied the regulatory role of the AP-1 transcription factor family in blood development using...

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Vydáno v:	Development (Cambridge) Ročník 143; číslo 23; s. 4324
Hlavní autoři:	Obier, Nadine, Cauchy, Pierre, Assi, Salam A, Gilmour, Jane, Lie-A-Ling, Michael, Lichtinger, Monika, Hoogenkamp, Maarten, Noailles, Laura, Cockerill, Peter N, Lacaud, Georges, Kouskoff, Valerie, Bonifer, Constanze
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England 01.12.2016
Témata:	Activating Transcription Factors - metabolism Animals Binding Sites - genetics Cell Differentiation - physiology Cell Line DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Embryonic Stem Cells - cytology Gene Expression - genetics Gene Expression Profiling Mice Muscle Proteins - metabolism Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Protein Binding Proto-Oncogene Proteins c-fos - metabolism Proto-Oncogene Proteins c-jun - metabolism Signal Transduction - physiology TEA Domain Transcription Factors Transcription Factor AP-1 - antagonists & inhibitors Transcription Factor AP-1 - metabolism Transcription Factors - metabolism TEAD4 ESC differentiation Signalling hubs Hematopoietic specification AP-1 Hippo signalling
ISSN:	1477-9129, 1477-9129
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Shrnutí:	The transmission of extracellular signals into the nucleus involves inducible transcription factors, but how different signalling pathways act in a cell type-specific fashion is poorly understood. Here, we studied the regulatory role of the AP-1 transcription factor family in blood development using embryonic stem cell differentiation coupled with genome-wide transcription factor binding and gene expression analyses. AP-1 factors respond to MAP kinase signalling and comprise dimers of FOS, ATF and JUN proteins. To examine genes regulated by AP-1 and to examine how it interacts with other inducible transcription factors, we abrogated its global DNA-binding activity using a dominant-negative FOS peptide. We show that FOS and JUN bind to and activate a specific set of vascular genes and that AP-1 inhibition shifts the balance between smooth muscle and hematopoietic differentiation towards blood. Furthermore, AP-1 is required for de novo binding of TEAD4, a transcription factor connected to Hippo signalling. Our bottom-up approach demonstrates that AP-1- and TEAD4-associated cis-regulatory elements form hubs for multiple signalling-responsive transcription factors and define the cistrome that regulates vascular and hematopoietic development by extrinsic signals.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1477-9129 1477-9129
DOI:	10.1242/dev.139857