Identification and characterization of a heme responsive element in the hrg-1 promoter

Abstract

Despite its biological significance, little is known about how animals sense and respond to heme to maintain homeostasis. C. elegans is a heme auxotroph, which makes it an excellent model to identify and dissect heme homeostasis pathways. Using C. elegans we have identified HRG-1, a vesicular heme transporter that is transcriptionally upregulated when environmental heme is low. The current study seeks to address how hrg-1 is regulated by heme. Here, we show that a putative 23 base pair (bp) heme-responsive element (HRE) and GATA-binding motifs are necessary for heme-dependent regulation of hrg-1. The HRE comprises both enhancer and repressor elements and works in conjunction with ELT-2 to regulate hrg-1 expression. We propose that the HRE could be used as a molecular tool in C. elegans to tightly regulate internal gene expression by modulating environmental heme. Our ultimate goal is to identify the trans-acting factor to eventually create a whole animal sensor for monitoring organismal heme homeostasis.