FACT and the proteasome promote promoter chromatin disassembly and transcriptional initiation.

The packaging of the eukaryotic genome into chromatin represses gene expression by blocking access of the general transcription machinery to the underlying DNA sequences. Accordingly, eukaryotes have developed a variety of mechanisms to disrupt, alter, or disassemble nucleosomes from promoter regions and open reading frames to allow transcription to occur. Although we know that chromatin disassembly from the yeast PHO5 promoter is triggered by the Pho4 activator, the mechanism is far from clear.

Acetylation in the globular core of histone H3 on lysine-56 promotes chromatin disassembly during transcriptional activation.

Promoter chromatin disassembly is a widely used mechanism to regulate eukaryotic transcriptional induction. Delaying histone H3/H4 removal from the yeast PHO5 promoter also leads to delayed removal of histones H2A/H2B, suggesting a constant equilibrium of assembly and disassembly of H2A/H2B, whereas H3/H4 disassembly is the highly regulated step. Toward understanding how H3/H4 disassembly is regulated, we observe a drastic increase in the levels of histone H3 acetylated on lysine-56 (K56ac) during promoter chromatin disassembly.

Chromatin disassembly from the PHO5 promoter is essential for the recruitment of the general transcription machinery and coactivators.

The disassembly of promoter nucleosomes appears to be a general property of highly transcribed eukaryotic genes. We have previously shown that the disassembly of chromatin from the promoters of the Saccharomyces cerevisiae PHO5 and PHO8 genes, mediated by the histone chaperone anti-silencing function 1 (Asf1), is essential for transcriptional activation upon phosphate depletion. This mechanism of transcriptional regulation is shared with the ADY2 and ADH2 genes upon glucose removal.

Transcriptional regulation by chromatin disassembly and reassembly.

The packaging of the eukaryotic genome into chromatin severely restricts the access of the transcriptional machinery to the DNA. Recent studies reveal that histones are removed and replaced to enable or restrict, respectively, access of the transcription machinery to regulate transcription. Chromatin disassembly at promoters enables transcriptional activation, whereas promoter chromatin reassembly represses transcription.