Zhang devised a biochemical strategy to isolate proteins that could remove methyl from histones inside a test tube. The result was the identification of a novel protein, JHDM1A, named for JmjC histone demethylase 1A. A similar protein exists in baker's yeast and has the potential to remove trimethyl groups.
JmjC is only a section of the entire JHDM1A protein, but is required for its demethylase activity. The authors showed that disruption of JmjC prevents JHDM1A from removing histone methyl groups.
Importantly, the JmjC section of JHDM1A, or "JmjC domain," can be found in other proteins, even when the proteins share little else in common. Database searches predict more than 100 total proteins found in organisms as diverse as bacteria and man contain the JmjC domain. This suggests that many other proteins may act similarly to methyl groups from histones or other proteins.
The implications of the new findings are as diverse as the proteins that contain a JmjC domain. For example, hair loss occurs in individuals with mutations in the JmjC domain of a protein called "hairless," possibly due to defects in the appropriate removal of histone methyl groups.
"Given the large numbers of JmjC domain-containing proteins that exist in diverse organisms ranging from yeast to human, our discovery will keep many people in the field busy for the years to come," said Zhang.