BLOCKING GENOME GATEKEEPERS

Abstract

A FAMILY OF ENZYMES KNOWN as histone deacetykses (HDACs) helps to regulate how and when our genome blueprint is transcribed and translated into protein. Small-molecule inhibitors of these enzymes are under intense investigation as cancer therapeutics, as evidenced by research presented last month in Honolulu at the 5th International Chemical Congress of Pacific Basin Societies (Pacifichem). Scientists described their efforts to create HDAC inhibitors for use as both drugs and probes of HDAC biology. Histone deacetylases remove acetyl groups from the histone-packing proteins around which genomic DNA is wrapped in the cell. The acetylation state of histones' lysine side chains helps orchestrate gene transcription: When acetylated, DNA wrapped histones unravel to give the cell's transcription machinery access to the DNA. Acetylation also acts to recruit this machinery When deacetylated, however, histones and DNA pack tightly together to prevent transcription. HDAC inhibitors thus trigger an increase in gene ...