TY - JOUR
T1 - Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth
AU - Dave, Kashyap
AU - Sur, Inderpreet
AU - Yan, Jian
AU - Zhang, Jilin
AU - Kaasinen, Eevi
AU - Zhong, Fan
AU - Blaas, Leander
AU - Li, Xiaoze
AU - Kharazi, Shabnam
AU - Gustafsson, Charlotte
AU - De Paepe, Ayla
AU - Månsson, Robert
AU - Taipale, Jussi
PY - 2017
Y1 - 2017
N2 - The gene desert upstream of the MYC oncogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer. 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. 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.
AB - The gene desert upstream of the MYC oncogene on chromosome 8q24 contains susceptibility loci for several major forms of human cancer. 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. 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.
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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85021072337&origin=recordpage
U2 - 10.7554/eLife.23382
DO - 10.7554/eLife.23382
M3 - RGC 21 - Publication in refereed journal
C2 - 28583252
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e23382
ER -