Heat shock factor 1 (HSF1) specifically potentiates c-MYC-mediated transcription independently of the canonical heat shock response

• DOI: 10.1016/j.celrep.2023.112557
• Publication Date: 2023-05-23T11:24:21Z
• Authors: Meng Xu; Ling Lin; Babul Moni Ram; Omprakash Shriwas; Kun-Han Chuang; Siyuan Dai; Kuo-Hui Su; Zijian Tang; Chengkai Dai
• Keywords: transcription factor complex; QH301-705.5; DNA; HSF1; Article; CUT&RUN-seq; DNA-Binding Proteins; Proto-Oncogene Proteins c-myc; c-MYC; Heat Shock Transcription Factors; Cell Line, Tumor; Humans; CP: Molecular biology; Biology (General); Heat-Shock Response; GCN5; Transcription Factors

Despite its pivotal roles in biology, how the transcriptional activity of c-MYC is tuned quantitatively remains poorly defined. Here, we show that heat shock factor 1 (HSF1), the master transcriptional regulator of the heat shock response, acts as a prime modifier of the c-MYC-mediated transcription. HSF1 deficiency diminishes c-MYC DNA binding and dampens its transcriptional activity genome wide. Mechanistically, c-MYC, MAX, and HSF1 assemble into a transcription factor complex on genomic DNAs, and surprisingly, the DNA binding of HSF1 is dispensable. Instead, HSF1 physically recruits the histone acetyltransferase general control nonderepressible 5 (GCN5), promoting histone acetylation and augmenting c-MYC transcriptional activity. Thus, we find that HSF1 specifically potentiates the c-MYC-mediated transcription, discrete from its canonical role in countering proteotoxic stress. Importantly, this mechanism of action engenders two distinct c-MYC activation states, primary and advanced, which may be important to accommodate diverse physiological and pathological conditions.