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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Bibliographic Details
Published in:Development (Cambridge) Vol. 143; no. 23; p. 4324
Main Authors: 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
Format: Journal Article
Language:English
Published: England 01.12.2016
Subjects:
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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Summary: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.
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ISSN:1477-9129
1477-9129
DOI:10.1242/dev.139857