-activation of small EDRK-rich factor 2 () promoter by Heat Shock Factor 1.

Heat shock response is an adaptive mechanism of cells characterized by rapid synthesis of a class of proteins popularly known as heat shock proteins (HSPs) by heat-induced activation of Heat Shock Factor 1 (HSF1). In course of our earlier study to show that HSF1 regulates transcription of HYPK (Huntingtin Yeast two-hybrid protein K), a chaperone-like protein, we observed presence of few other genes within 10 kb of promoter. In an attempt to understand whether adjacent genes of are co-regulated, we identified that (small EDRK-rich factor 2), an upstream neighboring gene of is also regulated by heat stress and HSF1. We also showed that promoter can be -activated by HSF1 due to the presence of functional heat shock element (HSE). Strikingly, is linked with through a Conjoined Gene (CG) albeit the respective proteins have opposite effect on mutant Huntingtin aggregates and subsequent toxicity. Our study provides the first report on regulation of expression and thereby depicts a paradigm where two parent genes of a CG are regulated by a common transcription factor despite the fact that they code for proteins having opposite cellular function in a given context.