Distinct layers of epigenetic regulation during prenatal development and postnatal maturation as well as in diseased human cardiac myocytes have been uncovered by University of Freiburg scientists.
The research team was led by Ralf Gilsbach and Lutz Hein from the Institute of Experimental and Clinical Pharmacology and Toxicology and the findings published recently in Nature Communications.
In order to locate all gene switches, the Freiburg research team used modern sequencing methods to examine the entire genome—DNA, epigenetic markers, and RNA—during the development, maturation, and disease of human cardiac muscle cells. By analyzing more than a trillion sequencing letters, the team found over 100,000 gene switches.
The multitude of data from the study provides a functional map of the non-coding genome of human cardiac myocytes throughout life. During development and growth, DNA methylation and histone markers control which genes are turned on or off. The atlas also provides insight into mechanisms that are misdirected in heart disease. Some regulatory elements are altered in cardiac arrhythmias at the DNA level, for example. In contrast, histones take control in chronic heart failure.
In the future, the Freiburg researchers want to identify the most important switches in this atlas in order to treat heart disease.