engleski

Yeast PHO Genes : An Excellent Model for Elucidation of Chromatin-Remodelling Mechanisms

Nucleosomes, the basic units of chromatin structure, repress transcription by restricting access of transcription factors to promoter cis-regulatory elements. It has recently become clearly evident that nucleosomes are highly dynamic and that there is, especially in yeast, a constant histone turnover mediated by a variety of chromatin-modifying and -remodelling multiprotein complexes. The yeast PHO5 promoter has been a very useful model in elucidating the relationship between chromatin structure remodelling and gene regulation, showing that chromatin remodelling is replication-independent and is not a consequence of, but a prerequisite for the gene transcription. Also, chromatin remodelling at the PHO5 promoter was the first in vivo demonstrated example of histone eviction in trans, a mechanism that operates also at the two other coregulated PHO promoters, PHO8 and PHO84, and has recently been revealed to occur genome-wide. Despite the fact that chromatin remodelling at all three promoters eventually leads to nucleosome disassembly, they show differential cofactor requirements. At the PHO5 promoter, an essential chromatin factor has not been identified yet and there is a redundancy of remodelling pathways involved. On the contrary, remodelling of the PHO8 nucleosomes is critically dependent on Snf2, but still another remodeller is involved as well. Interestingly, the two neighbouring nucleosomes at the PHO84 promoter demonstrate different stringency of remodeller dependency. Parallel in vitro studies of nucleosome stability and in vivo studies of cofactor requirements for their remodelling have shown that differential stringency of chromatin cofactor requirements is, at least to a large degree, determined by different intrinsic stabilities of individual promoter nucleosomes. As an already well characterized and established model system, the PHO promoters are a favourable system for parallel studies of remodelling events in vivo and mechanism of chromatin remodelling in vitro, which are of essential importance for our further understanding of the mechanisms of chromatin remodelling.

transcriptional regulation; chromatin remodelling; yeast PHO genes

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