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Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter-bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells.
Multicolor spectral analysis (spectral karyotyping) was applied to mitotic and male diakinetic chromosomes of hybrid mice carrying a unique system of 18 autosomal Robertsonian translocation chromosomes with alternating arm homologies. Only the autosomes 19 and the XY sex chromosomes are excluded from these Robertsonian translocations. The translocations, previously identified by conventional banding analyses, could be verified by spectral karyotyping. Besides the Robertsonian translocations, no other interchromosomal rearrangements were detected. In diakineses of male meiosis, the 18 metacentric Robertsonian translocation chromosomes form a very large meiotic ‘superring'. The predictable, specific order of the chromosomes along this ‘superring' was completely confirmed by multicolor spectral analysis. In the majority of diakineses analyzed, the free autosomal bivalent 19 and the XY sex bivalent form a conspicuous complex which tightly associates with the 12;14 Robertsonian translocation chromosome in the ‘superring'.