C-rel regulates inscuteable gene expression during mouse embryonic stem cell differentiation

Riki Ishibashi, Satoshi Kozuki, Sachiko Kamakura, Hideki Sumimoto, Fumiko Toyoshima

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Inscuteable (Insc) regulates cell fate decisions in several types of stem cells. Although it is recognized that the expression levels of mouse INSC govern the balance between symmetric and asymmetric stem cell division, regulation of mouse Insc gene expression remains poorly understood. Here, we showed that mouse Insc expression transiently increases at an early stage of differentiation, when mouse embryonic stem (mES) cells differentiate into bipotent mesendoderm capable of producing both endoderm and mesoderm in defined culture conditions. We identified theminimumtranscriptional regulatory element (354 bases) that drives mouse Insc transcription in mES cells within a region>5 kb upstream of the mouse Insc transcription start site. We found that the transcription factor reticuloendotheliosis oncogene (c-Rel) bound to the minimum element and promoted mouse Insc expression in mES cells. In addition, short interfering RNA-mediated knockdown of either mouse INSC or c-Rel protein decreased mesodermal cell populations without affecting differentiation into the mesendoderm or endoderm. Furthermore, overexpression of mouse INSC rescued the mesoderm- reduced phenotype induced by knockdown of c-Rel. We propose that regulation of mouse Insc expression by c-Rel modulates cell fate decisions during mES cell differentiation.

Original languageEnglish
Pages (from-to)3333-3345
Number of pages13
JournalJournal of Biological Chemistry
Volume291
Issue number7
DOIs
Publication statusPublished - Feb 12 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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