Craniofacial anomalies

Epigenetics and mental retardation

The classic DNA double helix spools around clusters of proteins called histones, whose antenna-like “tails” control access to different genes, extending the genetic code. Now, a team led by Yang Shi, PhD, in the Division of Newborn Medicine, shows that an enzyme that alters histones, known as a histone demethylase, may be a key player in a form of X-linked mental retardation affecting boys.

The genetic mutation behind the disorder, which also causes craniofacial defects, impairs this enzyme’s function. Modeling the disease in zebrafish, Shi and colleagues show that the enzyme normally works with a genetic partner to keep cells alive during brain development. When it’s mutated, the enzyme can’t sustain the gene’s activity. Brain cells die, and the fish are born without jaws.

When the enzyme’s activity was restored, brain cells survived and jaws were normal. It’s hard to judge a fish’s intelligence, but the researchers speculate that targeting this enzyme might also reverse cognitive impairment in X-linked mental retardation. (Nature online, July 11)