Boolean Gene Expression Map of the Brain: Logic of Expression

The basic genes of the human genome are mapped, and the gene variants that contribute to human disease are being mapped. That is a good start, but the really difficult work of understanding gene expression lies ahead. I am talking about the complex interactions of gene expression, and the many "maps" that must be compiled to detail gene expression. From MIT's Richard A.Young:

Each cell is the product of a specific gene expression program. Complex processes such as development of an organism from a single cell are the product of many cells executing many precise programs of gene expression in a temporally exact manner. These programs are controlled by transcriptional regulatory networks, and these networks are fundamental to all living processes. Such networks describe the factors that control the expression of each gene in the network, permitting the consequences of genetic or disease abnormalities to be analyzed in depth. Thus the eluciation of transcriptional regulatory networks in living organisms would be a substantial advance that could greatly contribute to the development of therapeutics and human health.

This recent newsrelease discusses the development of a Brain Gene Expression Map (BGEM) of the mouse at St. Jude Children's Research Hospital.

By St. Jude Children's Research Hospital, Scientists at St. Jude Children's Research Hospital have given investigators around the world free access to a powerful tool for studying brain development. The Internet-based tool, called the mouse Brain Gene Expression Map (BGEM), is one of the largest gene expression maps of an organ ever developed, according to the St. Jude researchers. They say the map will likely help scientists discover the genetic origins of brain cancers, which could speed development of novel drugs to treat them.

The continual updating and completion of the BGEM Web site will be crucial to scientists. More than half of the approximately 25,000 genes in the mouse are thought to be involved in the development and function of the nervous system, but scientists have determined the function of only 30 percent of them. Many brain disorders, such as tumors and some psychiatric diseases, are also believed to be caused by gene mutations that arise during development of this complex organ.

A report on the development and availability of the BGEM appears in the March 28 issue of PLoS Biology. The Web site is http://www.stjudebgem.org/

Read much more here.

Gene expression is far from straightforward. Not only do different genes interact in controlling each other, but each gene itself has differenct controller molecules and nucleotide segments, that interact in a Boolean fashion. This newsrelease discusses the Boolean nature of the regulation of gene expression:

It is easy to think of a gene acting like a light bulb, switching either on or off, remaining silent, or being transcribed by the RNA-making machinery. The region of DNA that controls the gene's output is called its regulatory region, and in this simple (and too simplistic) scenario, that region would act like a simple on–off switch.

But the regulatory regions of real genes are more complex, and act more like molecular computers, combining the effects of multiple inputs and calibrating the gene's output accordingly. The inputs are the various molecules that affect gene activity by binding to sites in the regulatory region. These molecules combine their effects in complex ways. Sometimes the gene remains silent unless both are present. Sometimes they are additive, such that the output when two factors are present is twice the output when only one is present. Sometimes they cancel each other out—in the presence of either, the gene is transcribed, but in the presence of both, it is not.

Thus, the regulatory region acts as a Boolean logic function, whose simple ANDs, ORs, and NOTs combine to determine the output of the gene. In a new study, Avi Mayo, Uri Alon, and colleagues show that mutations in the regulatory region affect this logic function in a simple and well-studied genetic system, the lac operon in Escherichia coli bacteria, whose suite of genes regulate metabolism of lactose.

Read more details at the source.

At Al Fin, we often discuss the introduction of genes into cells, to change gene expression. But it should be clear that there are many alternative mechanisms of changing gene expression, and scientists are a long way from both learning about and understanding them all.