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Essential dosage-dependent functions of the transcription factor yin yang 1 in late embryonic development and cell

El Bachir Affar1, Frédérique Gay, Yujiang Shi

  • 1Harvard Medical School, Department of Pathology, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Molecular and Cellular Biology
|April 14, 2006
PubMed

Insights

The Yin Yang 1 (YY1) transcription factor is crucial for embryonic development and cell proliferation. Reduced YY1 levels impair growth and viability, highlighting its dosage-dependent role in cell cycle control and apoptosis.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The Yin Yang 1 (YY1) transcription factor is essential for embryonic development, with its complete absence causing early lethality.
  • Understanding the precise roles and regulatory mechanisms of YY1 is critical for deciphering developmental processes and cellular functions.

Purpose of the Study:

  • To investigate the dosage-dependent requirement of YY1 during mammalian embryogenesis and cellular processes.
  • To elucidate the molecular mechanisms underlying YY1's functions in cell proliferation, cytokinesis, and apoptosis.

Main Methods:

  • Generation of knockout mice with varying YY1 expression levels using homologous recombination.
  • Phenotypic analysis of mutant embryos and mouse embryonic fibroblast (MEF) cells.
  • RNA interference-mediated inhibition of YY1 in HeLa cells.
  • Genome-wide expression profiling to identify YY1 target genes.

Main Results:

  • YY1 exhibits a dosage-dependent requirement for embryonic growth and viability, with reduced levels impairing development.
  • Lower YY1 levels correlate with decreased cell proliferation, while complete ablation causes cytokinesis failure and cell cycle arrest.
  • YY1 inhibition in HeLa cells leads to failed cytokinesis, proliferative arrest, and increased sensitivity to apoptotic stimuli.
  • Identification of numerous YY1 target genes involved in cell growth, proliferation, cytokinesis, apoptosis, development, and differentiation.

Conclusions:

  • YY1 plays a critical, dose-dependent role in regulating embryonic development, cell proliferation, and cytokinesis.
  • YY1 coordinates essential biological processes through a complex transcriptional network, impacting cell cycle control and apoptosis.
  • These findings provide insights into the molecular basis of YY1's developmental and cellular functions and broader mechanisms of eukaryotic cell regulation.

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