In a rare disorder, a familiar protein disrupts gene function

May 27, 2009

As reported this week in the open-access journal PLoS Biology, an international team of scientists studying a rare genetic disease has discovered that a bundle of proteins already known to be important for keeping chromosomes together also plays an important role in regulating gene expression in humans. In addition to shedding light on the biological roles of these proteins, the research may lead to the development of better diagnostic tools for Cornelia de Lange syndrome (CdLS), a multisystem developmental disease.

Ian D. Krantz, of The Children's Hospital of Philadelphia, and colleagues investigated cohesin, a protein complex consisting of at least four proteins that form a ring that encircles chromosomes during cell division. Cohesin's long-established "canonical" role is to control chromatids—the long strands that chromosomes form during . However, one open question in biology has been, "What does cohesin do when cells are not dividing?" The paper from Krantz's team provides part of the answer, as the first study in human cells to identify genes that are dysregulated when cohesin doesn't work properly. Cohesin's role in dysregulating has attracted considerable scientific interest with a recent discovery that it may also be implicated in cancer.

Using DNA microarrays, Krantz and colleagues did a genome-wide analysis of mutant cell lines from 16 patients with severe CdLS. All the cells had mutations in the NIPBL gene, which plays a role in moving cohesin onto and off , or in genes encoding components of the cohesin complex itself. The study team identified hundreds of genes that were dysregulated in patient samples compared to samples from healthy individuals, and also detected specific gene expression profiles that are unique to CdLS patients. Importantly, said Krantz, the expression levels of dysregulated genes corresponded to the severity of the disease.

"We found that gene expression is exquisitely regulated by cohesin and the NIBPL gene," said Krantz. "The gene expression patterns we found have great potential to be used in a for Cornelia de Lange syndrome." He added that gene profiling arrays have the potential to be developed as single-platform tools to diagnose, from a patient's blood sample, not only CdLS, but also a variety of other developmental disorders.

More information: Liu J, Zhang Z, Bando M, Itoh T, Deardorff MA, et al. (2009) Transcriptional Dysregulation in NIPBL and Cohesin Mutant . PLoS Biol 7(5):e1000119. doi:10.1371/journal.pbio.1000119,

Source: Public Library of Science (news : web)

Explore further: Coming together: tDNAs, RNA pol III and chromatid cohesion

Related Stories

New tool probes function of rice genes

October 9, 2008

A new tool for investigating the rice genome has been developed by researchers at UC Davis led by Pamela Ronald, professor of plant pathology. The inexpensive, publicly-available rice DNA microarray covers nearly all the ...

Suppressing cancer with a master control gene

February 23, 2009

Starting with the tiny fruit fly and then moving into mice and humans, researchers at VIB and K. U. Leuven show that expression of the same gene suppresses cancer in all three organisms. Reciprocally, switching off the gene ...

Cohesin jigsaw begins to fit

May 19, 2009

The essential chromosomal protein complex cohesin has crucial roles in sister chromatid cohesion, DNA repair and transcriptional regulation. Despite its conserved function, cohesin's disparate association patterns in different ...

Recommended for you

A better way to read the genome

October 9, 2015

UConn researchers have sequenced the RNA of the most complicated gene known in nature, using a hand-held sequencer no bigger than a cell phone.

Threat posed by 'pollen thief' bees uncovered

October 9, 2015

A new University of Stirling study has uncovered the secrets of 'pollen thief' bees - which take pollen from flowers but fail to act as effective pollinators - and the threat they pose to certain plant species.

Mapping the protein universe

October 9, 2015

To understand how life works, figure out the proteins first. DNA is the architect of life, but proteins are the workhorses. After proteins are built using DNA blueprints, they are constantly at work breaking down and building ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.