(PHILADELPHIA) -- At any given time, most of the roughly 30,000 genes that constitute the human genome are inactive, or repressed, closed to the cellular machinery that transcribes genes into the proteins of the body. In an average cell, only about one in ten genes is active, or expressed, at any given moment, with its DNA open to the cell' transcriptional machinery.
A dynamic cast of gatekeeper enzymes controls this access to the DNA, adding and removing particular molecules to open or close the genome to transcription as needed. Fully explicating the complex interplay among these enzymes and the molecules they manage has been a primary goal for scientists seeking to understand the mechanisms governing gene control. These mechanisms are vital for health-- when they go wrong, diseases like cancer can result.
In study published online February 22 in Cell, researchers at The Wistar Institute identify an important new player in this gene-control system, an enzyme responsible for removing certain molecules, or marks, involved in opening or closing chromatin, the material that makes up chromosomes. The activity of this enzyme is thought to be widespread in the genome, likely affecting many genes.
"This enzyme removes methyl groups from a specific location where they facilitate opening of the chromatin for gene expression, and therefore this enzyme maintains a repressed state of gene expression," says Ramin Shiekhattar, Ph.D., a professor at The Wistar Institute and senior author on the Cell study. Currently, Shiekhattar is also a professor at the Center de Regulacio Genomica in Barcelona. "When the enzyme is not present, however, the marks are not removed, and the chromatin remains open for transcription."
The enzyme, called JARID1d, is the first identified member of a new family of enzymes that removes trimethylation from histone H3 at the lysine 4 location. Histones are critical components of chromatin. In mammalian genomes, t
Contact: Franklin Hoke
The Wistar Institute