PA) -- (Philadelphia, PA) -- Scientists at the University
of Pennsylvania School of Medicine have identified
and described a small gene that regulates the delicate
balance involved in the healthy growth and replication
of heart muscle cells.
"This finding is likely to be important for our
understanding of the causes of congenital heart disease.
It is also relevant to our attempts to regrow damaged
heart muscle," said the corresponding author of
the study, Jonathan A. Epstein, MD, of Penn's
Departments of Medicine and Cell & Developmental
Biology. The study is scheduled to appear in the September
20 issue of the journal Cell.
The newly identified heart gene, Hop (an acronym for
homeodomain only protein), is a small protein
that lacks certain residues required for DNA binding,
but is activated early in fetal development and continues
modulating the expression of cardiac-specific genes
throughout life. Hop appears to bind directly to another
important regulator of development, serum response factor
(SRF), and block SRF from binding to DNA. By inhibiting
the expression of SRF, Hop protects cardiac muscle cells
from over-development, and from developing fatal abnormalities.
"There has been a lot of effort to try to determine
how SRF is regulated in different tissues," Epstein
said. "Now we see that Hop plays a vital part."
The study was funded by the National Institutes of Health,
the American Heart Association, and the W.W. Smith Foundation.
Others who participated in the research are: Fabian
Chen, MD; Hyun Kook, MD; Rita
Milewski, MD; Aaron D. Gitler, MD; Min
Min Lu, MD; Jun Li, MD; Ronniel Nazarian,
MD; Robert Schnepp, MD; Kuangyu Jen, MD;
Greg Runke, MD, and Mary C, Mullins, MD,
all of Penn; Christine Biben, MD; Joel P. Mackay, MD,
Jiri Novotny, MD, all of the Victor Chang Cardiac Research
Institute, Carlinghurst, Australia; Robert Schwartz,
MD, of Baylor College of Medicine, Houston, TX, and
Richard P. Harvey, MD, of the Chang Institute and the
University of New South Wales, Australia.
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