Genetics, Plant Biology
University of California, Los Angeles
Dr. Jacobsen is also a professor of molecular cell and developmental biology at the University of California, Los Angeles.
DNA Methylation and Gene Silencing
Plant biologist Steve Jacobsen has shown that the mild-mannered weed, Arabidopsis, is truly a super model for understanding DNA methylation, an important mechanism for regulating gene expression in developing organisms.
An organism's essential blueprint lies in the sequence of nucleotides that make up its genes, but their expression can be altered in many ways without changing the sequence information. Heritable changes in gene expression that do not modify the fundamental gene sequence are known as epigenetic gene regulation, and one of the primary ways cells do this is through DNA methylation. Cells can turn off, or silence, particular genes by chemically attaching methyl groups to their surface. This process is fundamental to controlling growth and development in both plant and animal cells and is important in some cancers: cancer cells silence tumor suppressor genes through methylation, and uncontrolled growth results.
Jacobsen, who grew up on a farm in Merced, California, had originally planned on working in applied plant science, but that vision changed when he studied Arabidopsis in graduate school; he is now recognized as a leading authority on DNA methylation.
Eukaryotic DNA methylation has been an enigma both because its function has been controversial and because it has been difficult in animal systems to understand how DNA methylation can be targeted to small regions of the genome. Jacobsen and others are gaining on this problem by studying the phenomenon of epigenetic mutationsalleles, or alternative forms, of developmentally important genes that have been silenced by DNA methylation. Methylation mutations can be used for classical genetic studies, because plants inherit them in the same patterns that they inherit genes.
Jacobsen is well known for studies of the CLARK KENT mutations in Arabidopsis, which affect the flower development gene SUPERMAN. Normally, the SUPERMAN gene makes sure that a flower produces only six stamens, the pollen-producing organs of the plant. Plants with a CLARK KENT mutation have an excessive number of stamens that are easy to see with the naked eye. Jacobsen showed that the CLARK KENT mutations were epigenetic variants of SUPERMAN and that they caused heavier methylation, which disrupted normal gene activity.
Jacobsen and his team later cloned three additional genes, CHROMOMETHYLASE3, KRYPTONITE (named, of course, because it weakens SUPERMAN and CLARK KENT), and ARGONAUTE4. Each reveals more about the mechanism of methylation and the interaction of methylated DNA with modified histones, proteins that help wrap up the DNA into tightly packed chromosomes, as well as with small RNAs molecules that target methylation.