Weill Institute researchers uncover basic cell pathway

By Krishna Ramanujan

Although all cells in an organism have the same DNA, cells function differently based on the genes they express. While most studies of gene expression focus on activities in the cell's nucleus, a new Cornell study finds that processes outside the nucleus -- along the cell membrane -- also play important roles in gene expression.

The study, published in the May 1 issue of , uses , a simple with 6,000 genes, most of which are found in other organisms, including humans, making them excellent candidates for studying complex biological pathways. This paper focuses on pathways related to the Gal1 gene, which is highly researched for characterizing as a model to understand how gene expression is induced and repressed.

The Cornell researchers identified two proteins, Tup1 and Cti6, which form a complex that regulates transcription of the Gal1 gene, but only through interactions with a lipid found on the cell membrane. Tup1 is highly conserved, meaning it has been unchanged through evolution and is found in many organisms from yeast to humans.

"People just focus on the chromosomes inside the nucleus [when studying gene expression]," said lead author Bong-Kwan Han, a research associate at Cornell's Weill Institute for Cell and Molecular Biology, who co-authored the paper with Scott Emr, director of the Weill Institute. "We show that we also have to look at the cytoplasm," Han added.

The researchers propose that Cti6 and a complex of the proteins Cyc8 and Tup1 shuttle out of the cell's nucleus to the , where they bind to a lipid called PI(3,5)P2 and then further assemble into a Cti6-Cyc8-Tup1 complex. This complex then shuttles back into the nucleus where it binds to other protein structures and plays central roles in activating and repressing transcription, and activating a repressed GAL1 gene.

"Our findings may provide important insights to understand how human Tup1 proteins regulate in our body," said Han. A few years ago, other researchers reported that the Charcot-Marie-Tooth disorder, a neurodegenerative human disease, may be related to a gene that regulates levels of the PI(3,5)P2 lipid. Also, since human Tup1 proteins are known to play an important role in nerve development, the researchers wonder whether the relationship between the PI(3,5)P2 lipid and Tup1 discovered in this study may be a factor in the underlying mechanism in the Charcot-Marie-Tooth disorder.

Future studies may explore whether such lipids modulate transcriptional regulators in other contexts and whether there are more examples of such lipid-mediated signaling mechanisms that shuttle between the cytoplasm to regulate the nucleus function of transcriptional factors.

Related Stories

Novel mechanism for control of gene expression revealed

Mar 04, 2011

Dr. David Levin, Professor of Molecular & Cell Biology at Boston University Henry M. Goldman School of Dental Medicine and Professor of Microbiology at Boston University School of Medicine discovered recently a novel, evolutionarily ...

Lipid involved with gene regulation uncovered

Sep 04, 2009

Virginia Commonwealth University School of Medicine researchers have discovered a new role for the bioactive lipid messenger, sphingosine-1-phosphate, or S1P, that is abundant in our blood - a finding that could lead to a ...

Lipid involved with gene regulation uncovered

Sep 08, 2009

(PhysOrg.com) -- Virginia Commonwealth University School of Medicine researchers have discovered a new role for the bioactive lipid messenger, sphingosine-1-phosphate, or S1P, that is abundant in our blood - a finding that ...

Recommended for you

Changes in scores of genes contribute to autism risk

Oct 29, 2014

Small differences in as many as a thousand genes contribute to risk for autism, according to a study led by Mount Sinai researchers and the Autism Sequencing Consortium (ASC), and published today in the journal Nature.

Dozens of genes associated with autism in new research

Oct 29, 2014

Two major genetic studies of autism, led in part by UC San Francisco scientists and involving more than 50 laboratories worldwide, have newly implicated dozens of genes in the disorder. The research shows ...

Genetic link to kidney stones identified

Oct 29, 2014

A new breakthrough could help kidney stone sufferers get an exact diagnosis and specific treatment after genetic links to the condition were identified.

User comments

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.