RT Journal Article SR Electronic T1 Mice deficient of Myc super-enhancer region reveal a differential control mechanism between normal and pathological growth JF bioRxiv FD Cold Spring Harbor Laboratory SP 082602 DO 10.1101/082602 A1 Kashyap Dave A1 Inderpreet Sur A1 Jian Yan A1 Jilin Zhang A1 Eevi Kaasinen A1 Fan Zhong A1 Leander Blaas A1 Xiaoze Li A1 Robert Månsson A1 Jussi Taipale YR 2016 UL http://biorxiv.org/content/early/2016/10/24/082602.abstract AB The gene desert upstream of the Myc oncogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer, including cancers of breast, prostate, and colon. The region shows high conservation between human and mouse and contains multiple MYC enhancers that are activated in tumor cells. However, the role of this region in normal development has not been addressed. Here we show that a 538 kb deletion of the entire MYC upstream super-enhancer region in mice results in 50 to 80% decrease in MYC expression in multiple tissues. The mice are viable and show no overt phenotype. However, they are resistant to tumorigenesis, and most normal cells isolated from them grow slowly in culture. Consistently, deletion of the 8q24 super-enhancer region perturbs Myc targets only in cultured cells, but not in vivo. These results reveal that only cells whose Myc activity is increased by serum or oncogenic driver mutations depend on the 8q24 super-enhancer region, and indicate that targeting the activity of this element is a promising strategy of cancer chemoprevention and therapy.