DNA is widely known as the primary map for a developing organism, giving directions about which proteins will or will not be produced. But recent studies have revealed a second layer of information acting on top of the DNA, a set of “epigenetic”  forces that are not caused by the underlying DNA sequence that further regulate gene expression. Chromatin looping is one such force. Another, called gene imprinting, is the result of physical and chemical additions to the DNA which allow either the maternally or paternally contributed gene to be expressed, but not both. Recent work from HSCI Executive Committee member Carla Kim introduces yet another list of directions for the DNA map when it comes to the role of imprinted genes. Kim and her team show that a protein called BMI1 regulates the expression of imprinted genes and that this regulation is necessary for the normal functioning of lung stem cell populations. Precise control of proteins encoded by imprinted genes was required for lung cell self-renewal and was lost in mutant cells that lacked BMI1. This greater understanding of lung stem cell regulation may, in the future, allow researchers to manipulate them to help treat injury and disease.  Kim’s work also shows that the regulation and function of imprinted genes is crucial to self-renewal mechanisms across a variety of tissue types.

Zacharek, S.; Fillmore, C.; Lau, A.; Gludish, D.; Chou, A.; Ho, J.; Zamponi, R.; Gazit, R.; Bock, C.; Jager, N.; Smith, Z.; Kim, T.; Saunders, A.; Wong, J.; Lee, J.; Roach, R.; Rossi, D.; Meissner, A.; Gimelbrant, A.; Park, P.; Kim, C. (2011) Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of Expression at Imprinted Loci. Cell Stem Cell 9, 272-281.