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Transcriptional repression of p27 is essential for murine embryonic development

Youichi Teratake1, Chisa Kuga1, Yuta Hasegawa1

  • 1Department of Biomedical Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba city, Chiba, Japan.

Scientific Reports
|May 20, 2016
PubMed

Insights

The Nczf gene, a transcriptional repressor, is essential for embryonic development. Its absence causes embryonic lethality by increasing p27 expression, a cell cycle inhibitor.

Area of Science:

  • Developmental Biology
  • Gene Regulation
  • Molecular Genetics

Background:

  • The Nczf gene encodes a KRAB zinc-finger protein, acting as a sequence-specific transcriptional repressor.
  • Nczf is identified as a target gene of Ncx, suggesting a role in cellular processes.

Purpose of the Study:

  • To investigate the function of Nczf in embryonic development.
  • To elucidate the molecular mechanisms underlying Nczf's role, particularly its regulation of cell cycle genes.

Main Methods:

  • Generation of Nczf knockout (Nczf-/-) mice.
  • Histopathological analysis and examination of cell cycle-related gene expression (p27).
  • Nczf knockdown using siRNA in mouse embryonic fibroblasts (MEFs) and p27 promoter luciferase reporter assays.

Main Results:

  • Nczf-/- mice exhibited embryonic lethality around E8.5, characterized by small body size and impaired axial rotation.
  • Histopathology showed decreased cell numbers and pyknotic cells in Nczf-/- embryos.
  • Nczf deficiency led to increased p27 expression, confirmed by siRNA knockdown and reporter gene assays.

Conclusions:

  • Nczf-mediated repression of p27 is crucial for normal embryonic development.
  • Restoration of survival and axial rotation in double knockout mice (Nczf-/-; p27-/-) highlights the critical role of the Nczf-p27 axis.

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