Molecular Complexes that Regulate Genes by Repression

The finding was published in the February 28, 2003, issue of the Journal of Biological Chemistry.

Normally a cell's DNA is intertwined with histone proteins in the highly structured chromatin, making it unavailable to the cellular machinery that would otherwise read its coded genetic information. Determination of specific cell and tissue types is controlled by the carefully regulated activation of selected sets of signature genes.

"One of the mysteries of gene expression is how different tissues in the body--heart, liver, brain--express the genes that are specific to them,” explained senior author Dr. Ramin Shiekhattar, an associate professor at The Wistar Institute (Philadelphia, PA, USA). "What really controls this? For a long time, people have been looking for the factors that activate these genes, but what we and others are learning is that the critical mechanism used to regulate entire sets of genes is actually repression.”

The current study describes molecular complexes that share two core subunits and appear to operate as co-repressors with a number of tissue-specific repressor molecules to maintain the gene-silencing structure of chromatin. One of the shared subunits is histone deacetylase (HDAC), known to repress gene activation by modifying chromatin structure. The second core subunit is called BHC110, which also appears to be an enzyme, although its specific activity remains to be determined.
"In some ways, it is like driving a car. You may not realize much driving relies on braking rather than acceleration. Without the brake, you cannot control the car,” said Dr. Shiekhattar.




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