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HSF1Base: a comprehensive database of HSF1 (heat shock factor 1) target genes

Dániel Kovács 1,*, Tímea Sigmond 1,*, Bernadette Hotzi 1,*, Balázs Bohár 1, Dávid Fazekas 1,2,3, Veronika Deák 4, Tibor Vellai 1,5,# and János Barna 1,5,#

1 Department of Genetics, Institute of Biology, Eötvös Loránd University, Pázmány Péter stny. 1/C, Budapest H-1117, Hungary

2 Earlham Institute, Norwich, United Kingdom

3 Quadram Institute, Norwich, United Kingdom

4 Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, University of Technology, Budapest, Hungary

5 MTA-ELTE Genetics Research Group, Eötvös Loránd University, Budapest, Hungary

* These authors contributed equally to this work

# Correspondence: vellai@falco.elte.hu and barna.janos@ttk.elte.hu; Tel.: +36-1-372-2500 Ext: 8684; Fax: +36-1-372-2641

Abstract: HSF1 (heat shock factor 1) is an evolutionarily conserved master transcriptional regulator of the heat shock response (HSR) in eukaryotic cells. In response to high temperatures, HSF1 upregulates genes encoding molecular chaperones, also called heat shock proteins, which assist damaged intracellular proteins to be refolded or degraded. Accumulating evidence reveals however that HSF1 is implicated in several other physiological and pathological processes such as differentiation, immune response and multidrug resistance, as well as in aging, neurodegenerative demise and cancer. To address how HSF1 participates in these processes one should systematically analyse its target genes. Here we present a novel database called HSF1Base (hsf1base.org) that contains a nearly comprehensive list of HSF1 target genes identified so far. The list was obtained by manually curating publications on individual HSF1 targets and analysing relevant high throughput transcriptomic and chromatin immunoprecipitation data derived from the literature and Yeastract database. To support the biological relevance of HSF1 targets identified by high throughput methods, we performed an enrichment analysis of (potential) HSF1 targets across different tissues/cell types and organisms. We found that general HSF1 functions (i.e., targets are expressed in all tissues/cell types) are mostly related to cellular proteostasis. Furthermore, HSF1 targets that are conserved across various animal taxa operate mostly in cellular stress pathways (e.g., autophagy), chromatin remodelling, ribosome biogenesis and aging. Together, these data highlight diverse roles for HSF1, expanding far beyond the HSR. Keywords: Ageing; Autophagy; Cell adhesion; Cell cycle; Circadian rhythm; Chromatin remodeling; Heat shock factor 1; Heat shock proteins; Heat shock response; Ribosome biogenesis