Disease relevance of HSE1

• Overexpression of yeast HSF strongly suppresses the null phenotype of the induced hsp82-delta HSE1 gene and re-establishes DNase I hypersensitivity over its promoter [1].

High impact information on HSE1

• These data support a model in which the Vps27p-Hse1p complex has multiple functions at the endosome, one of which is as a sorting receptor for ubiquitinated membrane proteins destined for degradation [2].
• Mutating either the TATA box or heat shock element 1 (HSE1) significantly reduced basal and heat-induced transcription while mutating both essentially inactivated expression [3].
• The HSF-HSE1 interaction is also critical for stimulating both basal (noninduced) and induced transcription [4].
• We propose that the remodeled chromatin phenotype previously shown for HSE1 point mutants (and lost in HSE1 deletion mutants) stems from the retention of productive, cooperative interactions between HSF and its target binding sites [4].
• Previous work has shown that heat shock factor (HSF) plays a central role in remodeling the chromatin structure of the yeast HSP82 promoter via constitutive interactions with its high-affinity binding site, heat shock element 1 (HSE1) [4].

Biological context of HSE1

• Distorted DNA structure is associated with each constitutively bound factor: protein binding to HSE1 appears to induce a local A-form-like helical conformation, whereas occupancy of the TATA box is associated with strand-specific nuclease hypersensitivity of an adjacent polypurine tract [5].
• In situ mutagenesis experiments indicate that HSE1 is absolutely required for both basal and induced expression, and that basal transcription can be preferentially abolished by point mutations within this sequence [5].
• Similar to HSE1 point mutants, we have found that basal transcription is preferentially repressed by an HMRE silencer element when it is transplaced approximately 1 kb upstream of the HSP82 start site [5].
• Genomic footprinting of the HSP82 promotor using chemical and enzymatic nucleases reveals that irrespective of transcriptional state, the most proximal of three heat shock elements, HSE1, is occupied along both sugar-phosphate backbones as well as within its major groove, while the TATA box is bound along both sugar-phosphate backbones [5].
• In this study, we examined the consequences of mutations in HSE1, HSE2, and HSE3 on HSF binding and transactivation [4].

Anatomical context of HSE1

• We describe a complex of Vps27p and Hse1p that localizes to endosomal compartments and is required for the recycling of Golgi proteins, formation of lumenal membranes and sorting of ubiquitinated proteins into those membranes [2].

Associations of HSE1 with chemical compounds

• Whereas the HSE1-associated factor binds tightly within the major groove of DNA, as discerned by protection of guanine residues from methylation by dimethyl sulfate in intact cells, the TATA factor appears to bind principally to the sugar-phosphate backbone, as revealed by strong protection from hydroxyl radical cleavage in whole-cell lysates [6].
• Protein binding to HSE1 appears to cause a non-B-conformation, on the basis of a local 12 base-pair periodicity of hydroxyl radical protection and the presence of multiple DNase I hyperreactive cleavages flanking HSE1, whose pattern changes following heat shock [6].
• Hse1, a Component of the Yeast Hrs-STAM Ubiquitin-sorting Complex, Associates with Ubiquitin Peptidases and a Ligase to Control Sorting Efficiency into Multivesicular Bodies [7].

Physical interactions of HSE1

• The GRF2-binding factor appears to facilitate the binding of proteins to both HSE1 and TATA, as these sequences, while still occupied, are less protected from in vivo dimethyl sulfate methylation in a deltaGRF2 strain [8].

Other interactions of HSE1

• HSE1, suggesting that the 10-fold higher basal transcription of HSC82 stems, at least in part, from a non-HSE-binding factor [5].
• Finally, deletion of a consensus upstream repressor sequence (URS1), positioned immediately upstream of the GRF2-HSE1 region and only weakly occupied in chromatin, has no expression phenotype, even under meiotic conditions [8].
• The results described here show that the noncanonical (or gapped) spacing of GAA units in the CUP1 HSE (HSE1) functions to limit the magnitude of CUP1 transcriptional activation in response to heat and oxidative stress [9].
• Based on our results we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and Hse1p in endosome protein sorting [10].

References