TY - JOUR
T1 - A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis
AU - Dietrich, Nicholas
AU - Schneider, Daniel L.
AU - Kornfeld, Kerry
N1 - Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2017/11/16
Y1 - 2017/11/16
N2 - The essential element zinc plays critical roles in biology. High zinc homeostasis mechanisms are beginning to be defined in animals, but low zinc homeostasis is poorly characterized. We investigated low zinc homeostasis in Caenorhabditis elegans because the genome encodes 14 evolutionarily conserved Zrt, Irt-like protein (ZIP) zinc transporter family members. Three C. elegans zipt genes were regulated in zinc-deficient conditions; these promoters contained an evolutionarily conserved motif that we named the low zinc activation (LZA) element that was both necessary and sufficient for activation of transcription in response to zinc deficiency. These results demonstrated that the LZA element is a critical part of the low zinc homeostasis pathway. Transcriptional regulation of the LZA element required the transcription factor ELT-2 and mediator complex member MDT-15. We investigated conservation in mammals by analyzing LZA element function in human cultured cells; the LZA element-mediated transcriptional activation in response to zinc deficiency in cells, suggesting a conserved pathway of low zinc homeostasis. We propose that the pathway for low zinc homeostasis, which includes the LZA element and ZIP transporters, acts in parallel to the pathway for high zinc homeostasis, which includes the HZA element, HIZR-1 transcription factor and cation diffusion facilitator transporters.
AB - The essential element zinc plays critical roles in biology. High zinc homeostasis mechanisms are beginning to be defined in animals, but low zinc homeostasis is poorly characterized. We investigated low zinc homeostasis in Caenorhabditis elegans because the genome encodes 14 evolutionarily conserved Zrt, Irt-like protein (ZIP) zinc transporter family members. Three C. elegans zipt genes were regulated in zinc-deficient conditions; these promoters contained an evolutionarily conserved motif that we named the low zinc activation (LZA) element that was both necessary and sufficient for activation of transcription in response to zinc deficiency. These results demonstrated that the LZA element is a critical part of the low zinc homeostasis pathway. Transcriptional regulation of the LZA element required the transcription factor ELT-2 and mediator complex member MDT-15. We investigated conservation in mammals by analyzing LZA element function in human cultured cells; the LZA element-mediated transcriptional activation in response to zinc deficiency in cells, suggesting a conserved pathway of low zinc homeostasis. We propose that the pathway for low zinc homeostasis, which includes the LZA element and ZIP transporters, acts in parallel to the pathway for high zinc homeostasis, which includes the HZA element, HIZR-1 transcription factor and cation diffusion facilitator transporters.
UR - http://www.scopus.com/inward/record.url?scp=85038242761&partnerID=8YFLogxK
U2 - 10.1093/nar/gkx762
DO - 10.1093/nar/gkx762
M3 - Article
C2 - 28977437
AN - SCOPUS:85038242761
SN - 0305-1048
VL - 45
SP - 11658
EP - 11672
JO - Nucleic acids research
JF - Nucleic acids research
IS - 20
ER -