Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness.

ABSTRACT: Hepcidin plays a major role in the regulation of iron homeostasis. Several bone morphogenetic proteins (BMPs) are strong inducers of hepcidin (Hamp1, HAMP) expression. Hemojuvelin, a protein critical for maintaining appropriate levels of hepcidin, acts as a coreceptor for BMP2 and BMP4, thereby providing a link between iron homeostasis and the BMP-signaling pathway. We show that a robust BMP, hemojuvelin, and SMAD1 response by murine Hamp1 is dependent on a distal BMP responsive element (BMP-RE2), the adjacent bZIP, HNF4alpha/COUP binding sites, and plus or minus 50 bp of the flanking area within -1.6 to -1.7 kb of the Hamp1 promoter. Furthermore, the STAT site and the BMP responsive element (BMP-RE1) located in the proximal 260-bp region of the Hamp1 promoter are also indispensable for ma

SUBMITTER: Truksa J 

PROVIDER: S-EPMC2628375 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature