Howard Cedar#
Short laudatio by Moshe Yaniv#
Howard Cedar has essentially discovered all of the basic biochemical mechanisms involved in DNA methylation and proven its biological role in vivo. He was the first to show that methyl groups are always symmetrically placed on both strands of the DNA at either CpG residues (in animal cells) or CpNpG residues (in plants). This symmetry serves as the basis for maintenance of methylation patterns following DNA synthesis utilizing an enzyme that specifically recognizes hemimethylated sites on newly replicated DNA. These findings demonstrated for the first time that epigenetic information can be copied in a manner similar to the DNA code itself using a fundamental semi-conservative mechanism.
Cedar was the first to demonstrate that DNA methylation is correlated with gene repression that housekeeping genes have constitutively unmethylated CpG islands, that it is the methyl groups themselves that inhibit transcription in vivo and that this is mediated through its effect on chromatin accessibility. In addition to these basic metabolic aspects of methylation, Cedar also showed that almost all methylation is erased in the early embryo and derived the molecular rules that explain how the overall pattern is re-established during development. He also deciphered the mechanism of this process.
These studies have set the groundwork for all subsequent research on DNA methylation in animals and plants. They have helped explain gene repression in general, genomic imprinting and X chromosome inactivation in females. DNA methylation is the basis for understanding the reprogramming that takes place in animal cloning and plays an important role in gene therapy and genetic engineering in plants. Abnormal de novo DNA methylation is responsible for Fragile X syndrome, the most universally prevalent form of mental retardation and plays a big role in shaping the oncogenic phenotype of cancer cells. Indeed it was Cedar’s lab that recently succeeded in actually deciphering the molecular logic of this process.
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