Friend of GATA suppresses the GATA-induced transcription of hepcidin in hepatocytes through a GATA-regulatory element in the HAMP promoter

摘要: Hepcidin is an antimicrobial peptide hormone involved in the metabolism of iron, encoded for by HAMP gene mainly hepatocytes. It's expressed at lower levels other cells such as macrophages. The mechanisms that determine tissue-specific expression hepcidin remain unclear. GATA- and its co-factor Friend GATA (FOG) modulate transcription genes iron. proteins are group evolutionary conserved transcriptional regulators bind to consensus motif -WGATAR- promoter. We characterized a 1.3 kb fragment 5'-flanking sequence Huh7 cells, which express HAMP. Transfection 5'-deletions promoter revealed two regions, -932/-878 -155/-96, when deleted decreased activity. Using site-directed mutations region -155/-96 we identified subregions, -138/-125 -103/-98, mutated suppressed activity 70 90% respectively. Site -103/-98 with -TTATCT- endogenous 4 6 transactivate GATA-regulatory element (RE). Mutation GATA-RE abrogated binding blunted transactivation FOG 1 2 exogenous activation concluded GATA-RE, crucial GATA-4 GATA-6 driven moderate suppressing