A modular system of DNA enhancer elements mediates tissue-specific activation of transcription by high dietary zinc in C. elegans

作者：Roh Hyun Cheol; Dimitrov Ivan; Deshmukh Krupa; Zhao Guoyan; Warnhoff Kurt; Cabrera Daniel; Tsai Wendy; Kornfeld Kerry^*

来源：Nucleic Acids Research, 2015, 43(2): 803-816.

DOI：10.1093/nar/gku1360

Zinc is essential for biological systems, and aberrant zinc metabolism is implicated in a broad range of human diseases. To maintain homeostasis in response to fluctuating levels of dietary zinc, animals regulate gene expression; however, mechanisms that mediate the transcriptional response to fluctuating levels of zinc have not been fully defined. Here, we identified DNA enhancer elements that mediate intestine-specific transcriptional activation in response to high levels of dietary zinc in C. elegans. Using bioin-formatics, we characterized an evolutionarily conserved enhancer element present in multiple zincinducible genes, the high zinc activation (HZA) element. The HZA was consistently adjacent to a GATA element that mediates expression in intestinal cells. Functional studies using transgenic animals demonstrated that this modular system of DNA enhancers mediates tissue-specific transcriptional activation in response to high levels of dietary zinc. We used this information to search the genome and successfully identified novel zinc-inducible genes. To characterize the mechanism of enhancer function, we demonstrated that the GATA transcription factor ELT-2 and the mediator subunit MDT-15 are necessary for zinc-responsive transcriptional activation. These findings define new mechanisms of zinc homeostasis and tissue-specific regulation of transcription.

• 出版日期2015-1-30