Distinct, Gene Specific Effect of Heat Shock on Heat Shock Factor‐1 Recruitment and Expression of CXC Chemokine Genes

Abstract

Earlier studies have shown that the stress‐activated transcription factor, heat shock factor‐1 (HSF1), modified expression of certain non‐HSP genes including cytokine and chemokine genes. An analysis of human and mouse CXC chemokine genes showed that 28 of the 29 genes had multiple putative heat shock response elements (HSEs) present in their promoters. To determine whether these potential HSEs were functional, we analyzed HSF1 recruitment and expression of 5 human CXC chemokine genes (CXCL‐1, 2, 3, 5 and 8) in heat shocked human lung epithelial‐like A549 cells. Chromatin immunoprecipitation (ChIP) analysis showed that HSF1 was recruited to all but one of these genes (CXCL‐3) and heat shock caused a significant increase in recruitment of HSF1 to one or multiple HSEs present in the promoters of CXCL‐1, 2, 5 and 8 genes. However, the effect of HS exposure on expression of these genes showed a variable gene‐specific effect. For example, CXCL8 expression was markedly enhanced (p<0.05) but CXCL5 expression was significantly repressed (p<0.05) in heat shocked A549 cells. In contrast, expression of CXCL1 and CXCL2, despite HSF1 recruitment to their promoters, was not affected by HS exposure. Our results indicate that some, if not all, putative HSEs present in the CXC chemokine gene promoters are functional and recruit HSF1 in vivo but the effects on gene expression are variable and gene specific.