Role of topoisomerase IIβ in the expression of developmentally regulated genes

Yi Lisa Lyu, Chao Po Lin, Anna M. Azarova, Li Cai, James C. Wang, Leroy F. Liu

研究成果: 雜誌貢獻文章同行評審

140 引文 斯高帕斯(Scopus)

摘要

Mice lacking topoisomerase IIβ (TopIIβ) are known to exhibit a perinatal death phenotype. In the current study, transcription profiles of the brains of wild-type and top2β knockout mouse embryos were generated. Surprisingly, only a small number (1 to 4%) of genes were affected in top2β knockout embryos. However, the expression of nearly 30% of developmentally regulated genes was either up- or down-regulated. By contrast, the expression of genes encoding general cell growth functions and early differentiation markers was not affected, suggesting that TopIIβ is not required for early differentiation programming but is specifically required for the expression of developmentally regulated genes at later stages of differentiation. Consistent with this notion, immunohistochemical analysis of brain sections showed that TopIIβ and histone deacetylase 2, a known TopIIβ-interacting protein, were preferentially expressed in neurons which are in their later stages of differentiation. Chromatin immunoprecipitation analysis of the developing brains revealed TopIIβ binding to the 5′ region of a number of TopIIβ-sensitive genes. Further studies of a TopIIβ-sensitive gene, Kcnd2, revealed the presence of TopIIβ in the transcription unit with major binding near the promoter region. Together, these results support a role of TopIIβ in activation/repression of developmentally regulated genes at late stages of neuronal differentiation.

原文英語
頁(從 - 到)7929-7941
頁數13
期刊Molecular and Cellular Biology
26
發行號21
DOIs
出版狀態已發佈 - 11月 2006
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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