Novel protein responsible for changing DNA structure and silencing the expression of genes identified

Oct 26 2009

A study published recently in the Proceedings of the National Academy of Science (PNAS) by a team of scientists headed by Professors Hélène Bierne and Pascale Cossart from the Pasteur Institute, in collaboration with colleagues form the CNRS and the French Agricultural Research Institute (INRA), identified a novel protein, BAHD1, which is responsible for changing DNA structure and silencing the expression of genes. Expression of pathological variants of genes may play a key role in causing various cancers and genetic disorders. The finding is part of the Spatelis research project, funded under the framework of ERA-NET PathoGenoMics, an initiative of the European Commission aimed at advancing transnational research in genome-based research programs on human-pathogenic microorganisms.

All the cells in any particular human body contain the same genetic information, and yet our body is made of very different cell types and tissues such as skin, brain or muscles. This is due to the fact that each cell type activates only a small subset of genes, rendering it unique and different from cell types. But how do cells "choose" what genes to turn on or off? They do so, among other means, by regulating the structure of chromatin, fibers made of DNA and proteins that constitutes our chromosomes. Chromatin may have tightly packed and condensed areas, where genes are silenced, or areas that are less densely packed and genes are activated. It is crucial to identify factors that regulate the chromatin structure since their alteration can lead to cancers, developmental abnormalities, and neurological disorders.

The protein identified by the French scientists, BAHD1, is such a factor, which behaves as a chromatin condensation machine at specific gene sites. In particular, BAHD1 silences IGF2, a gene mainly active during embryo development. This and other embryonic-development genes remain silent in healthy adults. However, in many human cancers these genes are inappropriately reactivated, causing the explosion of uncoordinated cell growth that is the hallmark of tumor formation.

"The discovery of the BAHD1 complex contributes to the understanding of how genes in cells of our body are regulated. Such knowledge could lead to new cancer therapies aimed at re-silencing inappropriately activated genes or to new prognosis markers," said Dr. Marion Karrasch-Bott, Coordinator of ERA-NET PathoGenoMics.