DNA oxidation drives Myc mediated transcription

Abstract

Myc oncogene is a transcription factor that contributes to the genesis of a wide variety of tumors by regulating proliferation, differentiation and apoptosis. Despite being one of the first isolated oncogene, the biochemical mechanisms of Myc mediated transcriptional regulation remain unclear. Myc has been found to govern different aspects of gene expression, from chromatin remodeling to basal transcription and processive RNAPII elongation. Myc binding to targets genes depends on the presence of the E-box binding motif and the presence of histone H3K4me3 lysines. Here, we summarize recent findings regarding the function of Myc in orchestrating different steps in transcription, and we propose a model that links histone H3 methylation code to Myc target genes. Myc upon binding to the E box triggers a series of events that assembles the transcription initiation complex, recruits the demethylating enzyme LSD1, induces DNA oxidation and chromating looping. Once started RNAPII still needs Myc assistance during transcription elongation. Myc seems to modulate at least two crucial steps in transcription. i.e., chromatin modifications for initiation and RNAPII pause release for productive elongation.