A copper transcription factor, AfMac1, regulates both iron and copper homeostasis in the opportunistic fungal pathogen Aspergillus fumigatus

Yong Sung Park, Suzie Kang, Hyewon Seo, Cheol-Won Yun

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of Aspergillus fumigatus, on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 50-TGTGCTCA-30 found in the promoter region of ctrC, the iron-specific AfMac1-binding motif 50-AT(C/G)NN(A/T)T(A/C)-30 was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of sit1 eliminated AfMac1-mediated sit1 up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and vice versa. AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions. Taken together, these results suggest that A. fumigatus independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions.

Original languageEnglish
Pages (from-to)2831-2845
Number of pages15
JournalBiochemical Journal
Volume475
Issue number17
DOIs
Publication statusPublished - 2018 Sep 11

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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