Gene That Regulates Development Of Heart Cells Identified, Described By Penn Researchers

"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.