S-phase progression mediates activation of a silenced gene in synthetic nuclei

Alison J. Crowe, Julie L. Piechan, Ling Sang, Michelle C. Barton

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Aberrant expression of developmentally silenced genes, characteristic of tumor cells and regenerating tissue, is highly correlated with increased cell proliferation. By modeling this process in vitro in synthetic nuclei, we find that DNA replication leads to deregulation of established developmental expression patterns. Chromatin assembly in the presence of adult mouse liver nuclear extract mediates developmental stage-specific silencing of the tumor marker gene alpha-fetoprotein (AFP). Replication of silenced AFP chromatin in synthetic nuclei depletes sequence-specific transcription repressors, thereby disrupting developmentally regulated repression. Hepatoma-derived factors can target partial derepression of AFP, but full transcription activation requires DNA replication. Thus, unscheduled entry into S phase directly mediates activation of a developmentally silenced gene by (i) depleting developmental stage-specific transcription repressors and (ii) facilitating binding of transactivators.

Original languageEnglish (US)
Pages (from-to)4169-4180
Number of pages12
JournalMolecular and cellular biology
Volume20
Issue number11
DOIs
StatePublished - Jun 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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