Abstract
Copper is a crucial trace element for all living systems and any deficiency in copper homeostasis leads to the development of severe diseases in humans. The observation of extensive evolutionary conservation in copper homeostatic systems between human and Saccharomyces cerevisiae made this organism a suitable model organism for elucidating molecular mechanisms of copper transport and homeostasis. In this study, the dynamic transcriptional response of both the reference strain and homozygous deletion mutant strain of CCC2, which encodes a Cu2+-transporting P-type ATPase, were investigated following the introduction of copper impulse to reach a copper concentration which was shown to improve the respiration capacity of CCC2 deletion mutants. The analysis of data by using different clustering algorithms revealed significantly affected processes and pathways in response to a switch from copper deficient environment to elevated copper levels. Sulfur compound, methionine and cysteine biosynthetic processes were identified as significantly affected processes for the first time in this study. Stress response, cellular response to DNA damage, iron ion homeostasis, ubiquitin dependent proteolysis, autophagy and regulation of macroautophagy, DNA repair and replication, as well as organization of mitochondrial respiratory chain complex IV, mitochondrial organization and translation were identified as significantly affected processes in only CCC2 deleted strain. The integration of the transcriptomic data with regulome revealed the differences in the extensive re-wiring of dynamic transcriptional organization and regulation in these strains.
Highlights
Of copper homeostasis in the nucleus provides evidence for the presence of changing copper concentrations in nucleus; there is still less known about copper transport into the n ucleus[4]
Dynamic transcriptional response of both the reference and CCC2 deleted strains of S. cerevisiae to a switch from copper deficient medium to elevated copper containing environment was investigated following the introduction of copper as an impulse at the steady-state
The dynamic transcriptional response of S. cerevisiae cells to a switch from copper deficient to copper rich environment was investigated by using different clustering methods and by integrating gene expression patterns with regulome
Summary
Of copper homeostasis in the nucleus provides evidence for the presence of changing copper concentrations in nucleus; there is still less known about copper transport into the n ucleus[4]. The collected dynamic transcriptional data was comparatively analyzed by using different clustering techniques based either on time dependent gene expression or co-expression profiles in order to identify the significantly affected biological processes and pathways in response to a switch from copper deficient environment to elevated copper levels. The integration of this data with regulome revealed the dynamic transcriptional and regulatory organization of the sets of genes in these two strains of S. cerevisiae in response to copper
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