May 2, 2009 — In an in vitro study, led by
Grace Gill, PhD, Tufts University School of Medicine, researchers
discovered how a protein called SUMO (Small Ubiquitin-related Modifier)
guides an enzyme complex that alters the structure of chromatin to
regulate expression of genes. Chromatin is a compacted mass of DNA and
protein that make up chromosomes.
The interaction between SUMO and the enzyme complex is of interest
in the study of cancer and neurodegenerative diseases such as
Alzheimer’s, where aberrant gene expression and altered SUMO function
are thought to be indicative of disease.
The protein called SUMO is known to chemically modify other
proteins, called transcription factors, which in turn enables the
meticulous regulation of genes. Gene regulation is a fundamental
biological process that allows necessary genes to be turned on or off
in specific cell types.
The researchers found that SUMO interacts with an enzyme complex
(LSD1/CoREST/HDAC) that alters chromatin structure to regulate genes
within cells. The researchers found that the interaction between SUMO
and this enzyme complex is responsible for preventing aberrant
expression. Aberrant gene expression is a common feature of cancer and
other disorders and altered SUMO processes might contribute to
"We’ve only known for about 10 years that SUMO chemically modifies
proteins. We have a good understanding of how SUMO modifies other
proteins, but the actual mechanism of how this modification alters cell
function is not well known. Our study uncovers a fundamental aspect of
how SUMO works, which has implications for many diseases. Until now,
SUMO and LSD1/CoREST/HDAC have not been studied together; we’ve found
out how they work together to turn off certain genes," says Gill.
The Gill Lab is continuing to investigate SUMO-dependent cell
activity to delineate the complex genetic mechanisms that support gene
First author Jian Ouyang, PhD, is a postdoctoral associate in Gill’s
lab, formerly in the department of pathology at Harvard Medical School.
Senior author Grace Gill, PhD, is an associate professor at Tufts
University School of Medicine and a member of the genetics and cell,
molecular and developmental biology program faculties at the Sackler
School of Graduate Biomedical Sciences at Tufts, formerly in the
department of pathology at Harvard Medical School.
This study was supported by an award from the Carolyn and Peter S.
Lynch Endowed Research Fund (to Harvard Medical School) and a grant
from the National Institute of General Medical Sciences at the National
Institutes of Health.