Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth

eLife

Charlotte Gustafsson¹  Robert Månsson¹  Ayla De Paepe¹  Shabnam Kharazi¹  Xiaoze Li¹  Leander Blaas²  Inderpreet Sur³  Kashyap Dave³  Jussi Taipale³  Jian Yan³  Fan Zhong³  Eevi Kaasinen³  Jilin Zhang³ 

[1] Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden;Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;

关键词: cancer;    oncogene regulation;    enhancer;   

DOI  :  10.7554/eLife.23382

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown