As an embryo is developing early on, cells and tissues for the person it will become are being formed for all time. These cells are molded into heart cells, skin cells, brain cells, and so on. Researchers are discovering that the epigenome is chiefly overseeing the works.
Epigenetic changes can help decide if genes are turned on or off. They can also affect the making of proteins in specific cells.
Researchers examining zebrafish embryos have demonstrated the epigenome plays a key role in steering development in the first day after fertilization.
"Our study suggests that an underappreciated fraction of the genome is involved in gene regulation," says senior author Ting Wang, PhD, assistant professor of genetics, Washington University School of Medicine in St Louis. "Another surprising finding is that many of the important regions of DNA we identified are pretty far away from the genes they regulate.
"The field long has been focused on identifying genes that manufacture proteins," Wang adds. "We are showing that the epigenome is just as important and is an area that is largely uncharted."
To think of it in computer-friendly terms, if our DNA code is hard-wired into our cells, the epigenome would be the software that makes sense of it. The DNA hardware would remain constant in each cell, but the differences in the epigenome differentiate one cell type from another.
With zebrafish as a model of vertebrate development, the study covers new ground in mapping changes in the epigenome of whole embryos and the part they play in gene regulation in the first hours of development.
"The human genome, like the zebrafish genome, is epigenetically regulated," Wang says. "But in humans, for ethical reasons, we can only look at tissues in childhood and adulthood and describe differences between cell types. With zebrafish, we can watch the developmental process as it unfolds."
The researchers have demonstrated that numerous developmental problems that produce the loss of the embryo via miscarriage or in later disorders, cannot be tied to a specific gene.
"This study suggests that many diseases may have an epigenetic origin," Wang says. "Even if there is nothing wrong with the protein coding genes themselves, there are lots of different regulatory changes that could mess up gene expression and lead to disease."
Wang says the findings back the trend of scientists who are discovering further noncoding parts of the genome that have an integral function in gene regulation.
"I'm sure there are parts of the genome for which we may never find a function," he says. "But when we look deep, we can derive very complex regulatory relationships between noncoding regions and the distant genes they regulate."
The research, titled "Developmental enhancers revealed by extensive DNA methylome maps of zebrafish early embryos," is found in the journal Nature Communications.