EVEN-SKIPPED HOMEOBOX 1 controls human ES cell differentiation by directly repressing GOOSECOID expression
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EVEN-SKIPPED HOMEOBOX 1 controls human ES cell differentiation by directly repressing GOOSECOID expression. / Kalisz, Mark; Winzi, Maria Karin; Bisgaard, Hanne Cathrine; Serup, Palle.
In: Developmental Biology, Vol. 362, No. 1, 01.02.2012, p. 94-103.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - EVEN-SKIPPED HOMEOBOX 1 controls human ES cell differentiation by directly repressing GOOSECOID expression
AU - Kalisz, Mark
AU - Winzi, Maria Karin
AU - Bisgaard, Hanne Cathrine
AU - Serup, Palle
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.ydbio.2011.11.017
DO - 10.1016/j.ydbio.2011.11.017
M3 - Journal article
C2 - 22178155
VL - 362
SP - 94
EP - 103
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 1
ER -
ID: 36074021