Genomics

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AP-1 and TEAD4 co-operatively promote the vascular program during hemangioblast specification [DNase-Seq]


ABSTRACT: Embryonic blood cell development occurs via well-defined developmental stages which are recapitulated in vitro by differentiation of embryonic stem cells. This process is tightly regulated by the interaction of tissue- specific and ubiquitous transcription factors with the chromatin landscape in response to outside signals. We previously identified binding motifs for the commonly expressed AP-1 transcription factor family in open chromatin regions specific for early stages of blood specification and thus aimed to study the role of AP-1 for hemangioblast differentiation. Here we show that FOS and JUN together bind to and activate a core set of vascular genes in the hemogenic endothelium and that upon global inhibition of AP-1 by expression of a dominant negative FOS peptide the balance between endothelial and hematopoietic fate is shifted towards blood. Moreover, we demonstrate that in the hemogenic endothelium AP-1 is required for de novo binding of TEAD4, a transcription factor connected to Hippo signaling, to vascular genes. Notably, after the endothelial-to-hematopoietic transition TEAD4 binding is no longer persisting. These findings provide novel mechanistic insights into vascular and hematopoietic development.

ORGANISM(S): Mus musculus

PROVIDER: GSE79321 | GEO | 2016/10/21

SECONDARY ACCESSION(S): PRJNA315456

REPOSITORIES: GEO

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