Key step in gene activation discovered

Scientists have cracked the code of an essential signal in the sequence of steps that controls the molecular choreography of gene regulation. The discovery is expected to aid development of therapies and prevention strategies for certain genetically triggered diseases such as breast cancers, pediatric cancers, and leukemia.

The research is published in a recent edition of the journal Cell by a Penn State team lead by Jerry L. Workman, the Paul Berg Professor of Biochemistry at Penn State and an associate investigator with the Howard Hughes Medical Institute, whose lab during the past few years has produced a series of discoveries that have dramatically altered the understanding of gene activation. The lab's latest achievement adds an important piece to the increasingly detailed picture of the individual feats performed by the menagerie of molecules that team up to turn genes on. The researchers have identified the communication code between two types of these molecules, which triggers them to begin the process of rearranging the shape of a gene, effectively unlocking its genetic code. One is a molecule nicknamed "SWI/SNF" and the other is a molecular family nicknamed the "HATs."

Like a pack of comicbook superheroes, each with a different power, the team of molecules that control the use of a gene's code has members with special skills and strange names. Inactive genes are locked in the "off" position by being densely coiled into structures called "Nucleosomes," which are built like a spool of thread, with the long strand of gene-containing DNA tightly wrapped around a spool-like core of powerful proteins called "Histones." The job of the Histones is to bind very strongly with the DNA strand, keeping it tightly coiled so its code can't be copied. "A normal cell turns on a particular gene only when it needs to produce a particular protein for a particular job at a particular time," Workman explains.

Each of the organism's many genes is distin

Contact: Barbara K. Kennedy
Penn State

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