Wolf Prize Laureate in Medicine 2008/9
Affiliation at the time of the award:
The Hebrew University of Jerusalem, Israel
“for their fundamental contributions to our understanding of the role of DNA methylation in the control of gene expression”.
The pioneering studies of Professor Howard Cedar and Professor Aharon Razin of the role of DNA methylation in the biological function of higher organisms has had widespread impact on studies in the fields of development, control of gene expression, epigenetics and cancer research. Their earliest experiments helped determine the patterns of DNA methylation in vivo, and their correlation with the suppression of gene expression. They then linked these methylation patterns to the recruitment of histone modifications associated with gene inactivation. In another extremely important contribution, they showed how DNA methylation patterns are laid down, erased, and reestablished in sperm, oocytes, and early embryonic development. These results are of the greatest significance for understanding the epigenetic transmission of expression patterns, particularly for imprinted genes, and are critical to the study of imprinting malfunctions in humans, which give rise to many congenital defects. The changes in methylation patterns are also critical events for the control of embryonic development, and their control will be essential in any extensive development of methods for exploiting the developmental potential of embryonic stem cells. There are also strong connections between their work and a major theme in cancer research, the marked de novo methylation of DNA cells. In summary, their experiments have been critical for establishing the fundamental role of DNA methylation in the control of gene expression.