Genomics researchers have found a role for DNA replication in inherited physical traits that is independent of changes in DNA sequencing. The study, which appeared in the journal Nature, was conducted by researchers at New York University, the University of California, Berkeley, and Cold Spring Harbor Laboratory.
Their finding is in the emerging field of epigenetics, which examines how changes in gene expression—caused by mechanisms other than alterations to the underlying DNA sequence—result in physical, or phenotypical, differences. Scientists have previously shown that these epigenetic phenomena are regulated by chemical modifications, such as methylation, of DNA and DNA-associated proteins, most notably histones. Alterations of these epigenetic modifications can lead to numerous diseases, such as cancer.
Biologists have historically sought to answer the question of how genetic information is inherited across generations. Several aspects of this phenomenon are well understood, mostly those involving changes in DNA sequences, in which chemical building blocks link up to form strands of genetic material. But less clear is how epigenetic information, namely specific modification of DNA, or histones, is passed from generation to generation.
To examine this question, the researchers for the Nature study examined epigenetic activity in fission yeast. Fission yeast provides a sound model for the study of epigenetic change as scientists can observe multiple generations in a short period of time. Furthermore, many epigenetic regulatory components in this organism are highly conserved and can also be found in humans. In this case, these researchers looked at the epigenetic regulation of heterochromatin, a highly compact and genetically inactive region of the genome. This inactive—or “silenced”—heterochromatin is mediated by a specific histone methylation mark, which is transmitted through generations.
In the Nature study, the researchers examined the role of a gene that regulates DNA replication, Cdc20, in controlling heterochromatin assembly and inheritance of the histone modification in heterochromatin. To understand Cdc20’s role in epigenetic regulation, the researchers investigated a mutant form of Cdc20, which, unlike normal Cdc20, fails to function at certain temperatures.
Their results showed that in order for heterochromatin to form and histone modification to be inherited properly, a normally functioning Cdc20 was required, thereby revealing the significance of the gene in epigenetic inheritance.
“Our results provide insight into how the epigenetic states of heterochromatin are faithfully duplicated in each cell cycle,” the researchers wrote. “Our findings suggest that DNA replication is required for heterochromatin assembly.”
The study’s authors were: Fei Li, an assistant professor at NYU’s Department of Biology; Rob Martienssen, a professor at Cold Spring Harbor Laboratory; and W. Zacheus Cande, a professor at the University of California, Berkeley’s Department of Molecular and Cell Biology.