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A pathological feature of Parkinson's disease is the presence of Lewy bodies within selectively vulnerable neurons. These are ubiquitinated cytoplasmic inclusions containing alpha-synuclein, an abundant protein normally associated with presynaptic terminals. Point mutations in the alpha-synuclein gene (A30P and A53T), as well as triplication of the(More)
We show that histone-DNA interactions are disrupted across entire yeast heat shock genes upon their transcriptional activation. At HSP82, nucleosomal disassembly spans a domain of approximately 3 kb, beginning upstream of the promoter and extending through the transcribed region. A kinetic analysis reveals that histone H4 loses contact with DNA within 45 s(More)
Chromatin is thought to repress transcription by limiting access of the DNA to transcription factors. Using a yeast heat shock gene flanked by mating-type silencers as a model system, we find that repressive, SIR-generated heterochromatin is permissive to the constitutive binding of an activator, HSF, and two components of the preinitiation complex (PIC),(More)
The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory(More)
In the nucleus, transcription factors must contend with the presence of chromatin in order to gain access to their cognate regulatory sequences. As most nuclear DNA is assembled into nucleosomes, activators must either invade a stable, preassembled nucleosome or preempt the formation of nucleosomes on newly replicated DNA, which is transiently free of(More)
Heat shock genes are poised for rapid transcriptional activation in response to environmental stress. A universal structural characteristic of such genes is the presence of a nucleosome-free, DNase I hypersensitive promoter region. Here we investigate the structural and functional effects of mutating HSE1, the preferred heat shock factor (HSF) binding site(More)
Transcription in eukaryotic cells occurs in the context of chromatin. Binding of sequence-specific regulatory factors must contend with the presence of nucleosomes for establishment of a committed preinitiation complex. Here we demonstrate that the high-affinity binding site for heat shock transcription factor (HSF) is occupied independently of other(More)
The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes because it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context-dependent, and the detailed mechanism by which it governs the expression of(More)
We report here that procedures commonly used to measure transcription and mRNA decay rates in Saccharomyces cerevisiae induce the heat shock response. First, conversion of cells to spheroplasts with lyticase, a prerequisite for nuclear runoff transcription, induces the expression of HSP70 and HSP90 heat shock genes. The transcript levels of the(More)