Here’s a strange question many people probably have not given much thought to: why are our faces shaped the way they are? We know that no two faces are perfectly alike, but why exactly might one person have a long nose and another a small forehead? How is it that our earlobes are attached to our ears and not our chins? Researchers from Switzerland and France have wondered this, and published a study in Science that suggests epigenetics might be a key player.
Filippo Rijli from Friedrich Miescher Institute for Biomedical Research, along with his team, discovered that epigenetic mechanisms known as histone modifications are involved in regulating face morphogenesis, or the biological process that creates the shape of one’s face. Even though genes controlling facial shape are nearly identical for every person, each face is interestingly unique.
When an embryo is in the early stages of development, the structure that consists of DNA wrapped around proteins, known as chromatin, maintains its plasticity in specialized cells. These particular cells are called neural crest cells, which go on to form different facial structures and give rise to most of the bones and cartilage of the face and skull.
Genes, at this point, are ready to respond to local cues. When particular environmental signals reach the neural crest, a switch occurs from a poised state to an active chromatin state. This begins position specific transcriptional programs that form the face.
Neural crest cells obtain a “positional” identity that is connected to their location in the face as it develops. As the cells migrate from the neural tube to the various areas of the head, the position identity is acquired. This identity is dependent on the interactions with the environment and the path which the cells take. Interestingly, the positional identity is not permanent even after migration, as neural crest cells are able to maintain some plasticity.
Rijli and his team, with the help of Michael Stadler, FMI computational biologist, have uncovered the details of how neural crest cells are able to maintain plasticity through migration, while also being ready to respond to environmental cues and begin the position-specific transcriptional programs which form the face. Ultimately, they found that this process is enabled by epigenetic regulation of chromatin organization.
“This is a novel conceptual framework for understanding how different facial features arise,” Rijli said about the team’s study. “Epigenetic poising may allow cranial neural crest cells to rapidly adapt their response to local variations in environmental signaling, thus potentially explaining differences in facial shape between individuals.”
Specifically, they looked at different chromatin profiles of neural crest cells in various positions prior to and after migration. First author Maryline Minoux said, “in the postmigratory neural crest cells, the promoters of the differentially silenced genes – i.e. genes not expressed in some populations, but expressed in others – were maintained in a bivalent configuration marked by both repressive H3K27me3 and activating H3K4me2 epigenetic histone modifications.”
The histone modifications poised the genes for activation. Interestingly, this configuration was already found in the neural crest cells before they had even begun migration. As soon as the cells are exposed to particular environmental cues, they get rid of the repressive H3K27 trimethylation mark (H3K27me3) and begin to form various facial features.
Additionally, the authors also discovered that the Ezh2 (Enhancer of zeste homolog 2) component of the PRC2 (Polycomb Repressive Complex 2) had a hand in regulating the poised chromatin state. PRC2 is an established chromatin remodeler during the embryo’s development.
Even if the genes responsible for these craniofacial structures are almost the same in each person, epigenetics could contribute to the reason why some people have a more pronounced forehead, high cheekbones, a button nose, or almond-shaped eyes. Although additional research is needed, the study offers novel insights into the epigenetic regulation of the formation of our facial features.
Source: Minoux M, et al. (2017). Gene bivalency at polycomb domains regulates cranial neural crest positional identity. Science, 355(6332).
Reference: Medical Xpress. Epigenetic regulation of face formation. 30 Mar 2017. Web.