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Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1
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Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1
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Journal Article
Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1
2006
Overview
Embryonic stem (ES) cells are pluripotent cells that can self-renew or differentiate into many cell types. A unique network of transcription factors and signalling molecules are essential for maintaining this capability. Here, we report that a
spalt
family member,
Sall4
, is required for the pluripotency of ES cells. Similarly to Oct4, a reduction in Sall4 levels in mouse ES cells results in respecification, under the appropriate culture conditions, of ES cells to the trophoblast lineage. Sall4 regulates transcription of
Pou5f1
which encodes Oct4. Sall4 binds to the highly conserved regulatory region of the
Pou5f1
distal enhancer and activates
Pou5f1
expression
in vivo
and
in vitro
. Microinjection of
Sall4
small interfering (si) RNA into mouse zygotes resulted in reduction of
Sall4
and
Oct4
mRNAs in preimplantation embryos and significant expansion of Cdx2 expression into the inner cell mass. These results demonstrate that Sall4 is a transcriptional activator of
Pou5f1
and has a critical role in the maintenance of ES cell pluripotency by modulating Oct4 expression. The data also indicates that Sall4 is important for early embryonic cell-fate decisions.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biology
/ Biomedical and Life Sciences
/ Chromatin Immunoprecipitation
/ Cloning
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - physiology
/ Electrophoretic Mobility Shift Assay
/ Embryo, Mammalian - cytology
/ Embryos
/ Female
/ Genes
/ Genomes
/ letter
/ Mice
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Pluripotent Stem Cells - metabolism
/ Sequence Homology, Nucleic Acid
/ Transcription Factors - genetics
