Researchers from the University of Geneva (UNIGE) and the Ecole polytechnique fédérale de Lausanne (EPFL), Switzerland recently uncovered novel information about how cells access promoter regions on DNA and accurately initiate the process of transcription. Studying the mechanisms that control and influence gene expression, the researchers were able to classify all promoters into two distinct types.
DNA Structure: Unraveling New Concepts
Our two-meter linear DNA is folded into millions of small packets that allow it to fit into each of our cells. These packets are called nucleosomes, and are often symbolized as ‘beads on a string’ which compact the DNA to a size of about 0.01mm in diameter. However, this packaging renders the DNA unreadable and the compact structure needs to be temporarily displaced for genes to be transcribed (copied) and translated into proteins.
Transcription starts with a promoter region, where the relevant enzyme attaches itself to initiate the process. The process that ensures proper access to promoter DNA was previously poorly understood. Researchers now claim that there are two different types of promoter regions that differ according to their state of nucleosome stability.
One type is characterized by the presence of unstable, dynamic nucleosomes, and is highly expressed in the genes associated with controlling cell growth and division. The second type contains well-documented stable nucleosomes, and is found relatively less often in expressed genes. The interaction between the different molecular factors involved in nucleosome destabilization is explained in the journal Molecular Cell.
Understanding Nucleosome Expression Using Yeast
“It is essential to understand how nucleosomes are moved, ejected or restructured. These translocations affect the accessibility of promoter DNA, which then influences the expression of corresponding genes”, explained David Shore, Professor at the Department of Molecular Biology of the Faculty of Science at UNIGE.
These dynamics – nucleosome formation and positioning in promoters – may help scientists understand why certain genes are highly expressed (normal or malignant growth) whereas others (stress-induced genes) are mostly rarely expressed under normal physiological conditions.
Discovering The ‘Fragile’ Nucleosome
Using yeast DNA as a model, since it closely resembles mammalian cells, the team of researchers characterized nucleosomes present in each of its gene promoter. Like human cells, yeast also contains the so-called ‘fragile’ nucleosomes. These nucleosomes are less resistant to the action of enzymes, however their function and nature remains a mystery.
“The two types of promoters we discovered differ by the presence of ‘fragile’ nucleosomes”, explained first author Slawomir Kubik, researcher at UNIGE. Moreover, the type of promoter containing ‘fragile’ nucleosomes was found to be significantly associated with high levels of transcription. Researchers speculate that the dynamic nature of this ‘fragile’ nucleosome plays an integral role enabling access of the proteins that initiate transcription to the promoter. “We believe that the presence of these dynamic nucleosomes in highly expressed genes helps to unwind the tightly coiled DNA efficiently and as often as necessary”, commented David Shore.