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• W2115987795 abstract "Precisely regulated expression of oncogenes and tumor suppressor genes is essential for normal development, and deregulated expression can lead to cancer. The human N-myc gene normally is expressed in only a subset of fetal epithelial tissues, and its expression is extinguished in all adult tissues except transiently in pre-B lymphocytes. The N-myc gene is overexpressed due to genomic amplification in the childhood tumor neuroblastoma. In previous work to investigate mechanisms of regulation of human N-mycgene expression, we observed that N-mycpromoter–chloramphemicol acelyltransferase reporter constructs containing sequences 5′ to exon 1 were active in all cell types examined, regardless of whether endogenous N-myc RNA was detected. In contrast, inclusion of the first exon and a portion of the first intron allowed expression only in those cell types with detectable endogenous N-myc transcripts. We investigated further the mechanisms by which this tissue-specific control of N-myc expression is achieved. Using nuclear run-on analyses, we determined that the N-myc gene is actively transcribed in all cell types examined, indicating a posttranscriptional mode of regulation. Using a series of N-myc intron 1 deletion constructs, we localized a 116-bp element (tissue-specific element [TSE]) within the first intron that directs tissue-specific N-myc expression. The TSE can function independently to regulate expression of a heterologous promoter-reporter minigene in a cell-specific pattern that mirrors the expression pattern of the endogenous N-myc gene. Surprisingly, the TSE can function in both sense and antisense orientations to regulate gene expression. Our data indicate that the human N-myc TSE functions through a posttranscriptional mechanism to regulate N-myc expression." @default.
• W2115987795 created "2016-06-24" @default.
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• W2115987795 date "1999-01-01" @default.
• W2115987795 modified "2023-09-27" @default.
• W2115987795 title "A Novel Intron Element Operates Posttranscriptionally To Regulate Human N-<i>myc</i> Expression" @default.
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• W2115987795 doi "https://doi.org/10.1128/mcb.19.1.155" @default.
• W2115987795 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/83874" @default.
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