engleski

Yeast PHO genes as an excellent model for elucidation of transcriptional regulation mechanism by chromatin remodeling

Nuclear eukaryotic DNA is packaged into nucleosomes which form the basic unit of a complex protein-nucleic acid structure termed chromatin. This packaging has a strong influence on the regulation of gene transcription as the accessibility of DNA regions, for example promoter elements and transactivator binding sites, is restricted and modulated by their incorporation into nucleosomes. There are several so called remodeling complexes, like the SWI/SNF complexes, that use the energy of ATP to slide nucleosomes along the DNA, alter the nucleosome structure to provide more DNA accessibility, exchange histones from the octamer core for variant histones, or even completely disassemble nucleosomes and evict the histones from the previously nucleosomal region. Remodeling complexes work in concert with a great variety of histone modifying enzymes that add or remove chemical modifications like acetyl-, methyl- or phosphate residues. At present it is not possible to predict which chromatin cofactors are required in a particular case of chromatin remodeling. The yeast PHO5 promoter is a classical example for the role of chromatin in promoter regulation. An array of four positioned nucleosomes at the promoter becomes mostly remodeled upon induction into an extended region that is largely depleted of histones. The PHO8 promoter is coregulated by the same transactivator as PHO5 and also shows a pronounced chromatin transition upon induction. However, the strong PHO5 promoter is less dependent on chromatin cofactors than the weaker PHO8 promoter. Recently, we turned to the PHO84 promoter which is coregulated with the PHO5 and PHO8 promoter but is even stronger than the PHO5 promoter. Interestingly, the two nucleosomes flanking the short hypersensitive region at this promoter in the repressed state, show a markedly different degree of cofactor requirement. This differential cofactor requirement correlates with different intrinsic stabilities of the two nucleosomes as determined in vitro. Therefore, the strong PHO84 promoter appears like a hybrid between the PHO5 and PHO8 promoters with regard to the presence of both a stable, strictly Snf2 dependent nucleosome and a less stable, redundantly remodeled nucleosome at the same promoter. We suggest that the differential cofactor requirement for remodeling of promoter nucleosomes is mainly determined by intrinsic features of individual nucleosomes and that promoter strength is not predictive for cofactor requirements.

transcriptional regulation; chromatin remodeling; histone modification; yeast PHO genes

nije evidentirano