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Genetic Enhancers Fine Tune Each Face

Article / Review by on November 18, 2013 – 6:55 pmNo Comments

Genetic Enhancers Fine Tune Each Face

Researchers identified thousands of genetic sequences that may help shape each person’s unique face. The findings may explain how our facial differences develop and lead to a new understanding of how facial birth defects arise.

Inherited genes are known to play a role in shaping a person’s face. Yet even family members have many subtle differences between them. Scientists have previously identified genes involved in birth defects such as cleft lips and palates. However, the factors responsible for normal, subtle facial differences are still largely unknown.

Genetic Enhancers Fine Tune Each Face

Genetic enhancers are short DNA sequences that control the activity levels of genes. These sequences are essentially docking sites for proteins that “enhance” the expression of their target genes through various mechanisms. Multiple enhancers can regulate the same gene from different locations on the genome. Variations in any of a gene’s enhancers can affect the gene’s activity level.

In previous work, Dr. Axel Visel of the Lawrence Berkeley National Laboratory and colleagues identified hundreds of enhancers that orchestrate gene expression during heart and brain development in embryos. In this study, Visel led a team to explore whether similar enhancers play a role in the development of facial features. Their work was funded in part by NIH’s National Institute of Dental and Craniofacial Research (NIDCR), National Human Genome Research Institute (NHGRI), and National Institute of General Medical Sciences (NIGMS). The results were published in Science on October 25, 2013.

First, the researchers searched for gene enhancers active in the facial tissue of mouse embryos at the time of face development. They identified candidate enhancers by finding regions of facial tissue DNA that were bound by enhancer-binding proteins. The team found more than 4,000 candidate enhancer sequences across the mouse genome.

The scientists selected 200 enhancers for further characterization. For each, they engineered mouse embryos to show a distinct color in facial areas where the enhancer was active. Images of the developing faces showed that different enhancers affected different facial regions. For example, one enhancer was active in the areas on either side of the nose, whereas another was active near the upper lip and nose. Most of these characterized sequences are also found in the human genome.

The researchers directly tested whether 3 of the enhancers affected the shape of the facial regions where they were active. They deleted the enhancers and then compared precise skull measurements of the mice to those of normal mice. None of the deletions caused obvious deformities. Two of the deletions were associated with subtle but significant changes in the facial regions where the enhancer was previously shown to be active.

“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.

The team is now working with human geneticists to explore whether mutations of human enhancer sequences similar to those found in the mouse genome are linked to facial birth defects in people.

By Katherine Wendelsdorf, Ph.D.

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*  The above story is reprinted from materials provided by National Institutes of Health (NIH)
** The National Institutes of Health (NIH) , a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency—making important discoveries that improve health and save lives. The National Institutes of Health is made up of 27 different components called Institutes and Centers. Each has its own specific research agenda. All but three of these components receive their funding directly from Congress, and administrate their own budgets.

More about National Institutes of Health (NIH)

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