Gene Enhancers Play Major Role In Making Our Faces Unique
October 25, 2013

Gene Enhancers Play Major Role In Making Our Faces Unique

[ Watch the Video: Face It - We All Look Different ]

April Flowers for - Your Universe Online

No two faces look exactly alike, making the human face as unique as a fingerprint.

What makes facial morphology so distinct, though? Genetics obviously plays a major role, as is evident in the similarities between parents and children. But what in our DNA fine-tunes the genetics so that siblings, especially identical twins, resemble one another but look different from unrelated individuals?

A new study from the US Department of Energy's Lawrence Berkeley National Laboratory (LBNL) has demonstrated that gene enhancers -- regulatory sequences of DNA that act to turn on or amplify the expression of a specific gene – are major players in craniofacial development.

"Our results suggest it is likely there are thousands of enhancers in the human genome that are somehow involved in craniofacial development," says Axel Visel, a geneticist with Berkeley Lab's Genomics Division. "We don't know yet what all of these enhancers do, but we do know that they are out there and they are important for craniofacial development."

Some genetic defects responsible for craniofacial pathologies such as clefts of the lip or palate have been identified. However, the genetic drivers of normal craniofacial variation are poorly understood.

Visel and colleagues mapped gene enhancers in the heart, brain and other organ systems in prior studies, demonstrating that gene enhancers can regulate their targets from across distances of hundreds of thousands of base pairs. An international team of scientists joined Visel in studying transgenic mice to determine if gene enhancers can have the same long-distance impact on craniofacial development. Their findings were published in a recent episode of Science.

"We used a combination of epigenomic profiling, in vivo characterization of candidate enhancer sequences, and targeted deletion experiments to examine the role of distant-acting enhancers in the craniofacial development of our mice," says Catia Attanasio. "This enabled us to identify complex regulatory landscapes, consisting of enhancers that drive spatially complex developmental expression patterns. Analysis of mouse lines in which individual craniofacial enhancers had been deleted revealed significant alterations of craniofacial shape, demonstrating the functional importance of enhancers in defining face and skull morphology."

More than 4,000 candidate enhancer sequences predicted to be active in fine-tuning the expression of genes involved in craniofacial development were identified by the team, who also created genome-wide maps of these enhancers by pin-pointing their location in the mouse genome. The activity of some 200 of these gene enhancers were characterized in detail by the researchers who deleted three of them. Most of the enhancer sequences identified and mapped are at least partially conserved between humans and mice. Many of these are located in human chromosomal regions associated with normal facial morphology or craniofacial birth defects.

"Knowing about the existence of these enhancers, which are inherited from parents to their children just like genes, knowing their exact location in the human genome, and knowing their general activity pattern in craniofacial development should facilitate a better understanding of the connection between genetics and human craniofacial morphology," Visel says. "Our results also offer an opportunity for human geneticists to look for mutations specifically in enhancers that may play a role in birth defects, which in turn may help to develop better diagnostic and therapeutic approaches."

The team is in the process of refining their genome-wide maps to gain more data about the activity patterns of these enhancer sequences. They are collaborating with human geneticists to conduct targeted searches for mutations of these enhancer sequences in human patients who have craniofacial birth defects.