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PMID:21062744

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Citation

Karantzali, E, Lekakis, V, Ioannou, M, Hadjimichael, C, Papamatheakis, J and Kretsovali, A (2011) Sall1 regulates embryonic stem cell differentiation in association with nanog. J. Biol. Chem. 286:1037-45

Abstract

Sall1 is a multi-zinc finger transcription factor that regulates kidney organogenesis. It is considered to be a transcriptional repressor, preferentially localized on heterochromatin. Mutations or deletions of the human SALL1 gene are associated with the Townes-Brocks syndrome. Despite its high expression, no function was yet assigned for Sall1 in embryonic stem (ES) cells. In the present study, we show that Sall1 is expressed in a differentiation-dependent manner and physically interacts with Nanog and Sox2, two components of the core pluripotency network. Genome-wide mapping of Sall1-binding loci has identified 591 genes, 80% of which are also targeted by Nanog. A large proportion of these genes are related to self-renewal and differentiation. Sall1 positively regulates and synergizes with Nanog for gene transcriptional regulation. In addition, our data show that Sall1 suppresses the ectodermal and mesodermal differentiation. Specifically, the induction of the gastrulation markers T brachyury, Goosecoid, and Dkk1 and the neuroectodermal markers Otx2 and Hand1 was inhibited by Sall1 overexpression during embryoid body differentiation. These data demonstrate a novel role for Sall1 as a member of the transcriptional network that regulates stem cell pluripotency.

Links

PubMed PMC3020710 Online version:10.1074/jbc.M110.170050

Keywords

Cell Differentiation/physiology; Chromatin/physiology; Embryonic Stem Cells/cytology; Embryonic Stem Cells/physiology; Gene Expression Regulation, Developmental; HEK293 Cells; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Humans; Oligonucleotide Array Sequence Analysis; Pluripotent Stem Cells/cytology; Pluripotent Stem Cells/physiology; SOXB1 Transcription Factors/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SOX2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ER74

F

Seeded From UniProt

complete

MOUSE:NANOG

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ER74

F

Seeded From UniProt

complete

MOUSE:NANOG

enables

GO:0000987: cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0000165)

Seeded From UniProt

complete

MOUSE:SALL1

located_in

GO:0005634: nucleus

ECO:0000305: curator inference used in manual assertion

GO:0000987

C

Seeded From UniProt

complete

MOUSE:SALL1

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SALL1

enables

GO:0000987: cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0000165)

Seeded From UniProt

complete

MOUSE:SALL1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P48432

F

Seeded From UniProt

complete

MOUSE:SALL1

enables

GO:0001085: RNA polymerase II transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q80Z64

F

Seeded From UniProt

complete

MOUSE:SALL1

involved_in

GO:2000384: negative regulation of ectoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SALL1

involved_in

GO:2000381: negative regulation of mesoderm development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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