Meet Genetics' Master Chefs

ACCESSION NO:  93-94-2627
       TITLE:  Meet Genetics' Master Chefs
      AUTHOR:  SCHMIDT, KAREN
     JOURNAL:  New Scientist
    CITATION:  April 23, 1994, 142(1922): 32-35.
        YEAR:  1994
    PUB TYPE:  Article
 IDENTIFIERS:  TRANSCRIPTION FACTORS; DNA; RNA; GENE EXPRESSION; 
               CHROMOSOMES; GENETIC DISEASES; PROTEIN MOLECULES

ABSTRACT: Transcription factors, protein molecules that bind to DNA with the effect of switching genes on or off, have become one of the hottest topics in molecular biology. Many scientists hope to gain control of gene expression as a strategy for treating such diseases as cancer and human immunodeficiency virus (HIV).

Studies show that at least 1,000, and perhaps as many as 10,000 of the estimated 100,000 genes that make up the genome of a typical mammal (the total complement of all hereditary factors), may encode transcription factors. Another discovery is that different transcription factors can collaborate to produce a particular effect on a gene.

Researchers have identified several hundred transcription factors in yeast cells and mammals, including humans, that function similarly. The defining characteristic of these proteins is that they all have structures called "DNA-binding domains." These allow proteins to recognize a particular stretch of DNA and dock into the groove between its two nucleotide strands (the basic chemical unit comprising DNA and RNA). Scientists have uncovered the shapes of these molecules and have classified them into families with names that reflect the shape of the protein including leucine zippers, helix-loop-helix proteins and zinc fingers. The leucine zipper proteins have helped researchers understand how transcription factors can collaborate to produce a range of different effects on genes. Research also indicates that it is the overall shape and size of a molecular complex, not those of its protein pieces, that decides which gene is switched on.

Researchers also suspect that the way genes are packaged influences transcription. In cell nuclei, DNA is not only double-stranded and helical, it is also wrapped around large, globular proteins called nucleosomes. Numerous other proteins also help stabilize the DNA and build up the chromosome. Biologists are just beginning to look at whether interactions with these proteins could make some genes more accessible than others to transcription. Evidence already exists that the tagging of a gene with methyl chemical groups can shield it against transcription and result in "genomic imprinting." Insights into human biology and medicine are now beginning to emerge. Some genetic diseases including certain types of leukemia and syndromes that affect nervous system development have been linked to defects in homedomain transcription factors.

Additional studies of laboratory mice, which share with humans a similar pattern of four rows of homeobox-containing genes, each one on a separate chromosome, are necessary.