New research from the Strahl lab at UNC has established a link between histone H3 lysine 9 methylation and DNA methylation in humans

Mouse embryonic stem cells (blue, green) lose DNA methylation (red) in the absence of UHRF1. Source: Brian D Strahl Lab, UNC School of Medicine

CHAPEL HILL, N.C. – Over the last two decades, scientists have come to understand that the genetic code held within DNA represents only part of the blueprint of life. The rest comes from specific patterns of chemical tags that overlay the DNA structure, determining how tightly the DNA is packaged and how accessible certain genes are to be switched on or off.

As researchers have uncovered more and more of these “epigenetic” tags, they have begun to wonder how they are all connected. Now, research from Brian D. Strahl’s group at UNC has established a new link between two epigenetic modifications — histone H3 lysine 9 methylation and DNA methylation — in humans.

The study, which was published Sept. 30, 2012 by the journal Nature Structural & Molecular Biology, implicates a protein called UHRF1 in the maintenance of these epigenetic tags. Because the protein has been found to be defective in cancer, the finding could help scientists understand not only how microscopic chemical changes can ultimately affect the epigenetic landscape but also give clues to the underlying causes of disease and cancer.

“There’s always been the suspicion that regions marked by DNA methylation might be maintained by H3 lysine 9 methylation, and that has even been shown to be true in model organisms like fungus and plants,” said senior study author Brian D Strahl, PhD, associate professor of biochemistry and biophysics in the University of North Carolina School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center. “But no one has been able to make that leap in human cells. It’s been controversial in terms of whether or not there’s really a connection. We have shown there is.”

Brian Strahl, along with his postdoctoral fellow Scott Rothbart, honed in on this discovery by using a highly sophisticated technique developed in his lab known as next generation peptide arrays. First the Strahl lab generated specific types of histone modifications and dotted them on tiny glass slides called “arrays.” They then used these “arrays” to see how histone modifications affected the docking of different proteins. One protein – UHRF1 – stood out because it bound a specific histone modification (lysine 9 methylation on histone H3) in cases where others could not.

Strahl and his colleagues focused the rest of their experiments on understanding the role of UHRF1 binding to this histone modification. They found that while other proteins that dock on this epigenetic tag are ejected during a specific phase of the cell cycle, mitosis, UHRF1 sticks around. Importantly, the protein’s association with histones throughout the cell cycle appears to be critical to maintaining another epigenetic tag called DNA methylation.  The result was surprising because researchers had previously believed that the maintenance of DNA methylation occurred exclusively during a single step of the cell cycle called DNA replication.

“This role of UHRF1 outside of DNA replication is certainly unexpected, but I think it is just another way of making sure we don’t lose information about our epigenetic landscape,” said Strahl.

The research was funded by the National Institutes of Health and the North Carolina Biotechnology Center.

Study co-authors from UNC were Scott B. Rothbart, PhD, a postdoc in Brian D. Strahl’s lab at UNC; Krzysztof Krajewski, PhD, research assistant professor; and Jorge Y. Martinez, a former student in Strahl’s lab.

Media contact: Tom Hughes, (919) 966-6047, tahughes@unch.unc.edu

Advertisements

About drbrianstrahl

Brian David Strahl, a Professor of Biochemistry and Biophysics at The University of North Carolina at Chapel Hill (UNC), started his research lab in 2001. His research areas include cancer biology, epigenetics and gene regulation. At UNC, Dr. Strahl provides instruction to undergraduate, graduate, and postdoctoral students in his laboratory. Over the years, Brian Strahl has received a number of important awards for his work in the field of gene expression and epigenetics. In 2009, he received the Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement from UNC. In 2008, the National Institutes of Health awarded him a EUREKA (Exceptional, Unconventional Research Enabling Knowledge Acceleration). His alma mater, the University of North Carolina at Greensboro, awarded him a Young Alumni Award in 2006 for scientific achievement. Brian Strahl has also won the ASBMB Schering-Plough Research Institute Award, a major biomedical award. In 2003, Dr. Strahl was honored by the White House for his achievements and was awarded a Presidential Early Career Award for Scientists and Engineers. In 2004, Brian was a PEW Scholar in Biomedical Sciences. Dr. Strahl is a member of several professional organizations, including the American Society for Microbiology and the American Society of Biochemistry and Molecular Biology.
This entry was posted in Uncategorized and tagged , , , , , , . Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s