EVEN-SKIPPED HOMEOBOX 1 controls human ES cell differentiation by directly repressing GOOSECOID expression

Mark Kalisz, Maria Karin Winzi, Hanne Cathrine Bisgaard, Palle Serup

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22 Citationer (Scopus)

Abstract

TGFß signaling patterns the primitive streak, yet little is known about transcriptional effectors that mediate the cell fate choices during streak-like development in mammalian embryos and in embryonic stem (ES) cells. Here we demonstrate that cross-antagonistic actions of EVEN-SKIPPED HOMEOBOX 1 (EVX1) and GOOSECOID (GSC) regulate cell fate decisions in streak-like progenitors derived from human ES cells exposed to BMP4 and/or activin. We found that EVX1 repressed GSC expression and promoted formation of posterior streak-like progeny in response to BMP4, and conversely that GSC repressed EVX1 expression and was required for development of anterior streak-like progeny in response to activin. Chromatin immunoprecipitation assays showed that EVX1 bound to the GSC 5'-flanking region in BMP4 treated human ES cells, and band shift assays identified two EVX1 binding sites in the GSC 5'-region. Significantly, we found that intact EVX1 binding sites were required for BMP4-mediated repression of GSC reporter constructs. We conclude that BMP4-induced EVX1 repress GSC directly and the two genes form the core of a gene regulatory network (GRN) controlling cell fates in streak-like human ES cell progeny.
OriginalsprogEngelsk
TidsskriftDevelopmental Biology
Vol/bind362
Udgave nummer1
Sider (fra-til)94-103
Antal sider10
ISSN0012-1606
DOI
StatusUdgivet - 1 feb. 2012

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