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EnglishN-Myc is a transcription factor that forms heterodimers with the protein Max and binds gene promoters by recognizing a DNA sequence, CACGTG, called E-box. The identification of N-myc target genes is an important step for understanding N-Myc biological functions in both physiological and pathological contexts. In this study, we describe the identification of N-Myc-responsive genes through chromatin immunoprecipitation and methylationsensitive restriction analysis. Results show that N-Myc is a direct regulator of several identified genes, and that methylation of the CpG dinucleotide within the E-box prevents the access of N-Myc to gene promoters in vivo. Furthermore, methylation profile of the E-box within the promoters of EGFR and CASP8, two genes directly controlled by Myc, is cell type-specific, suggesting that differential E-box methylation may contribute to generating unique patterns of Myc-dependent transcription. This study illuminates a central role of DNA methylation in controlling N-Myc occupancy at gene promoters and modulating its transcriptional activity in cancer cells.
| Titolo: | In vivo transcriptional regulation of N-Myc target genes is controlled by E-box methylation | |
| Autore/i: | PERINI, GIOVANNI; DIOLAITI, DANIEL; PORRO, ANTONIO; DELLA VALLE, GIULIANO | |
| Autore/i Unibo: | ||
| Anno: | 2005 | |
| Rivista: | ||
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1073/pnas.0409097102 | |
| Abstract: | N-Myc is a transcription factor that forms heterodimers with the protein Max and binds gene promoters by recognizing a DNA sequence, CACGTG, called E-box. The identification of N-myc target genes is an important step for understanding N-Myc biological functions in both physiological and pathological contexts. In this study, we describe the identification of N-Myc-responsive genes through chromatin immunoprecipitation and methylationsensitive restriction analysis. Results show that N-Myc is a direct regulator of several identified genes, and that methylation of the CpG dinucleotide within the E-box prevents the access of N-Myc to gene promoters in vivo. Furthermore, methylation profile of the E-box within the promoters of EGFR and CASP8, two genes directly controlled by Myc, is cell type-specific, suggesting that differential E-box methylation may contribute to generating unique patterns of Myc-dependent transcription. This study illuminates a central role of DNA methylation in controlling N-Myc occupancy at gene promoters and modulating its transcriptional activity in cancer cells. | |
| Data prodotto definitivo in UGOV: | 2005-10-11 21:28:07 | |
| Data stato definitivo: | 2016-08-05T12:25:23Z | |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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