Correlation of dysfunction of nonmuscle myosin IIA with increased induction of Cyp1a1 in Hepa-1 cells

Masayuki Ebina, Masahiko Shibazaki, Kyoko Kudo, Shuya Kasai, Hideaki Kikuchi

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    The aryl hydrocarbon receptor (AhR) is one of the best known ligand-activated transcription factors and it induces Cyp1a1 transcription by binding with 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). Recent focus has been on the relationship of AhR with signaling pathways that modulate cell shape and migration. In nonmuscle cells, nonmuscle myosin II is one of the key determinants of cell morphology, but it has not been investigated whether its function is related to Cyp1a1 induction. In this study, we observed that (-)-blebbistatin, which is a specific inhibitor of nonmuscle myosin II, increased the level of CYP1A1-mRNA in Hepa-1 cells. Comparison of (-)-blebbistatin with (+)-blebbistatin, which is an inactive enantiomer, indicated that the increase of CYP1A1-mRNA was due to nonmuscle myosin II inhibition. Subsequent knockdown experiments observed that reduction of nonmuscle myosin IIA, which is only an isoform of nonmuscle myosin II expressed in Hepa-1 cells, was related to the enhancement of TCDD-dependent Cyp1a1 induction. Moreover, chromatin immunoprecipitation assay indicated that the increase of Cyp1a1 induction was the result of transcriptional activation due to increased binding of AhR and RNA polymerase II to the enhancer and proximal promoter regions of Cyp1a1, respectively. These findings provide a new insight into the correlation between the function of nonmuscle myosin II and gene induction.

    Original languageEnglish
    Pages (from-to)176-183
    Number of pages8
    JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
    Volume1809
    Issue number3
    DOIs
    Publication statusPublished - 2011 Mar 1

    Keywords

    • AhR
    • NMIIA
    • TCDD
    • Transcription

    ASJC Scopus subject areas

    • Biophysics
    • Structural Biology
    • Biochemistry
    • Molecular Biology
    • Genetics

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