Small heat shock proteins are induced by various stresses. The C. elegans genome contains 4 major HSP-16 proteins. Two of the
hsp-16 genes in C. elegans responded to hypoxia, while the other two genes, which share the promoter regions with their counterparts, did not. Phylogenic analysis of the 10 C. briggsae
hsp-16 genes with C. elegans
hsp-16 genes established that the HSP-16 family could be classified into two classes: the HSP-16.1 class and the HSP-16.41 class. The genes that show orientation-specific hypoxia responses are contained within the HSP-16.1 class. The comparison of the promoter sequences of HSP-16.1 class revealed a new conserved regulatory element (block I) consisting of CAC(A/T)CT that was required for the orientation-dependent hypoxia response, but not for other stress responses such as heat or ethanol. This orientation-dependent hypoxia response of
hsp-16 is independent of HIF-1, a hypoxia inducible factor, indicating that its induction may be mediated by a new mechanism. HMG-1.2, a high mobility group box-containing protein, was identified as a block I binding protein. Downregulation of
hmg-1.2 by RNAi led to suppression of
hsp-16.1 induction under hypoxia. Among genes that are predicted to interact with HMG-1.2, proteins involved in chromatin structures were involved in
hsp-16.1 induction at the hypoxic condition. It is possible that the chromatin remodeling process is involved in hypoxia response of
hsp-16.1.