cellular and mouse models of Huntington’s disease the cyclic AMP-PKA signaling axis was decreased in the early stages of illness [28]. This effect may involve trapping of factors such as p300 and CBP in inclusions derived from aggregated poly-Q and inhibition of transcription factor CREB [29]. HSF1 is regulated in a comparable way to CREB, through stable PKA binding and, as shown here recruitment of p300, and may be likewise a target in the progression of Huntington’s disease (Fig. 2, 3). Indeed, in Drosophila, expression of CREB and Hsp70 additively suppress polyglutamine-mediated toxicity [30]. Supporting Information Figure S1 HSF1 associates with p300 and pTEFb after heat shock. This is a lower magnification image (63X) of cells treated as in Fig. 1A–D in the main text. Experiments were carried out in duplicate reproducibly. (TIF) Figure S2 ChIP analysis of HSF1, RNA Pol II and Pol II phospho-S2 association with the pHuR98nc locus in non- heat-shocked cells or after 45 min at 426C. 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