Autoregulation of the N-myc gene is operative in neuroblastoma and involves histone deacetylase 2

Cancer
Marianne K H Kim, William L Carroll

Abstract

Autoregulation of the myc gene family is a negative feedback mechanism known to occur at high levels of Myc expression. Loss of this mechanism and associated Myc overexpression has been observed in human tumors, thereby contributing to tumorigenesis. The childhood tumor neuroblastoma is characterized by N-myc amplification in aggressive and highly proliferative tumors that occur in a subset of patients. The precise molecular mechanism of autoregulation is unknown, and previous observations indicated that N-myc autoregulation was intact only in single-copy neuroblastoma cell lines. Transient reporter assays and trichostatin A (TSA) experiments were performed to evaluate several candidate genes, including Mxi1, c-myc promoter binding protein 1 (MBP-1), Miz, and histone deacetylase 2 (HDAC2), for their involvement in N-myc autoregulation. Mxi1 and HDAC2 were examined further for their expression levels and effects on endogenous N-myc levels. Finally, their recruitments to the N-myc promoter were investigated by chromatin immunoprecipitation (ChIP). The autoregulatory circuit was operative, even in amplified cell lines. Mxi1 consistently showed a modest effect in down-regulating N-myc in transient reporter assays. Overexpression of...Continue Reading

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Citations

Jan 31, 2012·Molecules and Cells·In-Young HwangHong-Duk Youn
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