The Zinc Finger Protein ZNF658 Regulates the Transcription of Genes Involved in Zinc Homeostasis and Affects Ribosome Biogenesis through the Zinc Transcriptional Regulatory Element
| Autor: | Alison Howard, Ogo A. Ogo, Simon Cockell, John Tyson, Ruth A. Valentine, Dianne Ford |
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| Rok vydání: | 2015 |
| Předmět: |
Small interfering RNA
Saccharomyces cerevisiae Proteins Transcription Genetic Molecular Sequence Data Gene Expression Ribosome biogenesis chemistry.chemical_element Saccharomyces cerevisiae Zinc Biology DNA-binding protein Cell Line Tumor Gene expression Transcriptional regulation Homeostasis Humans Electrophoretic mobility shift assay Amino Acid Sequence Regulatory Elements Transcriptional Promoter Regions Genetic Molecular Biology Zinc finger Binding Sites C100 Zinc Fingers Articles Cell Biology C700 Molecular biology Cell biology DNA-Binding Proteins chemistry Caco-2 Cells Ribosomes |
| Zdroj: | Molecular and Cellular Biology |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.01298-14 |
| Popis: | We previously identified the ZTRE (zinc transcriptional regulatory element) in genes involved in zinc homeostasis and showed that it mediates transcriptional repression in response to zinc. We now report that ZNF658 acts at the ZTRE. ZNF658 was identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry of a band excised after electrophoretic mobility shift assay using a ZTRE probe. The protein contains a KRAB domain and 21 zinc fingers. It has similarity with ZAP1 from Saccharomyces cerevisiae, which regulates the response to zinc restriction, including a conserved DNA binding region we show to be functional also in ZNF658. Small interfering RNA (siRNA) targeted to ZNF658 abrogated the zinc-induced, ZTRE-dependent reduction in SLC30A5 (ZnT5 gene), SLC30A10 (ZnT10 gene), and CBWD transcripts in human Caco-2 cells and the ability of zinc to repress reporter gene expression from corresponding promoter-reporter constructs. Microarray analysis of the effect of reducing ZNF658 expression by siRNA uncovered a large decrease in rRNA. We find that ZTREs are clustered within the 45S rRNA precursor. We also saw effects on expression of multiple ribosomal proteins. ZNF658 thus links zinc homeostasis with ribosome biogenesis, the most active transcriptional, and hence zinc-demanding, process in the cell. ZNF658 is thus a novel transcriptional regulator that plays a fundamental role in the orchestrated cellular response to zinc availability. |
| Databáze: | OpenAIRE |
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