Opening and closing the genome

Feb 22, 2007

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, trimethyl groups at the lysine 4 location of this histone have been known to be associated with gene activation. Shiekhattar and his team hypothesized the existence of an enzyme that would remove these trimethyl groups.

"We and others had wondered whether there might not be an enzyme able to remove these trimethyl marks," says Shiekhattar. "Such an enzyme would have the effect of setting the genes back to their original repressed state."

An important aspect of the work by Shiekhattar and his colleagues is their demonstration of an intimate connection between the histone demethylase enzyme JARID1d and Ring6a, a polycomb-like protein. Polycomb proteins are also known to play an important role in gene repression. Indeed, the findings show that Ring6a has the ability to regulate the enzymatic activity of the histone demethylase in vitro as well as in vivo. These results extend the role of transcriptional inhibitory polycomb complexes through their physical and functional link with histone demethylase enzymes.

Source: The Wistar Institute

Explore further: Friction harnessed by proteins helps organize cell division

add to favorites email to friend print save as pdf

Related Stories

Enzyme controls transport of genomic building blocks

Mar 06, 2014

Our DNA and its architecture are duplicated every time our cells divide. Histone proteins are key building blocks of this architecture and contain crucial information that regulates our genes. Danish researchers ...

New application of physics tools used in biology

Feb 07, 2014

A Lawrence Livermore National Laboratory physicist and his colleagues have found a new application for the tools and mathematics typically used in physics to help solve problems in biology.

Recommended for you

Gene removal could have implications beyond plant science

20 minutes ago

(Phys.org) —For thousands of years humans have been tinkering with plant genetics, even when they didn't realize that is what they were doing, in an effort to make stronger, healthier crops that endured climates better, ...

Lemurs match scent of a friend to sound of her voice

12 hours ago

Humans aren't alone in their ability to match a voice to a face—animals such as dogs, horses, crows and monkeys are able to recognize familiar individuals this way too, a growing body of research shows.

User comments : 0

More news stories

Gene removal could have implications beyond plant science

(Phys.org) —For thousands of years humans have been tinkering with plant genetics, even when they didn't realize that is what they were doing, in an effort to make stronger, healthier crops that endured climates better, ...

Making 'bucky-balls' in spin-out's sights

(Phys.org) —A new Oxford spin-out firm is targeting the difficult challenge of manufacturing fullerenes, known as 'bucky-balls' because of their spherical shape, a type of carbon nanomaterial which, like ...