MYC Transcriptomics

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MYC is a transcriptional factor and a proto-oncogene that is frequently deregulated in a wide array of cancers. Myc family genes include MYC, MYCN and MYCL1, which encode nuclear phospho proteins and function as sequence specific transcription factors that regulate large number of genes. All the MYC family members have been implicated in a wide variety of human hematological malignancies and solid tumors. Of all the Myc family proteins, the MYC transcription factor is extensively studied and has been defined as a global regulator. The genome wide location analysis and gene expression profiling disclosed that 15% of the genome is regulated by the MYC transcription factor. Alterations in MYC expression are induced by multiple mechanisms, including translocations, gene amplification, point mutations, over expression and increased protein stability. The MYC regulated cellular processes include cell growth, proliferation, differentiation, cell cycle progression, cell metabolism and apoptosis. The recent studies demonstrate that MYC is also a master regulator of ribosome biogenesis.

Many cancer cells have elevated levels of the MYC transcription factor, and it directly impacts the tumor progression. How does the elevated levels of MYC regulates the transcription of vast number of genes is an interesting question to understand as targeting MYC in MYC dependent tumors appears to be an appealing strategy. Deregulated MYC expression is suggested to induce a transcriptional response network that is different from the response triggered by endogenous level of MYC, which is fully re-strained by feedback loops. Transcriptomic analysis of MYC binding sites can reveal the global regulation of MYC transcription factor. Two recent studies demonstrated that in tumor cells expressing high levels of MYC, the transcription factor accumulates at elevated levels in association with its heterodimer partner, Max at the E-box sequences of core promoter region of the actively transcribed genes and enhances the transcripts levels of the active genes [5,6]. In addition to the core promoter, the MYC also binds to enhancer sequences of active genes. This shows that MYC is not an on-off specifier of specific transcriptional programs, but rather a universal amplifier of gene expression increasing output from all active promoters. The increased transcripts levels were achieved by stimulation of RNA Pol II elongation.

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Transcriptomics: Open Access
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