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 (
hsp-16.1 and
hsp-16.2) in C. elegans responded to hypoxia, while the other two genes (
hsp-16.48 and
hsp-16.41), which share the promoter regions with their counterparts, did not. The comparison of the promoter sequences of
hsp-16.1 revealed a new conserved regulatory element (block I) consisting of CAC(A/T)CT that was required for the hypoxia response, but not for other stress responses such as heat or ethanol. This hypoxia response of
hsp-16.1 does not require
hif-1 function, 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 responsible for
hsp-16.1 induction at the hypoxic condition. It has been demonstrated that
tax-6, an ortholog of Calcineurin A, was induced by hypoxia in a
hif-1-independent manner. Others have shown that hypoxia induced intracellular Ca2+ and that HIF-1 is not involved in Ca2+-dependent activation of hypoxia genes. Reduction function of
tax-6 decreased the hypoxia response of
hsp-16.1. Relatively little is known about regulatory pathways independent of HIF. It is possible that the calcium signaling and chromatin remodeling process are involved in
hif-1-independent hypoxia response of
hsp-16.1.