Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide Ifh1p occupancy at the OX growth phase and RC quiescent phase of the yeast metabolic cycle

ABSTRACT: We found ribosomal transcription factor Ifh1p is dynamically acetylated and phosphorylated in response to nutrient cues. ChIP-seq data revealed dynamic binding to ribosomal genes (RP) during the OX growth phase of the yeast metabolic cycle (YMC) when RP genes are highly induced, and weaker binding in the RC quiescent-like phase. Besides RP genes, our ChIP-seq data also reveals binding of Ifh1p to non-RP genes such as translation factors and metabolic genes. Examination of Ifh1p binding over two timepoints of the YMC (OX, RC) using Input as the control.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Ling Cai

PROVIDER: E-GEOD-39147 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease. To identify a common cellular response to primary RC that might improve mechanistic understanding and lead to targeted therapies for human RC disease, we performed collective transcriptome profiling in skeletal muscle biopsy specimens and fibroblast cell lines (FCLs) of a diverse cohort of human mitochondrial disease subjects relative to controls. Systems biology investigations of common cellular responses to primary RC disease revealed a collective pattern of transcriptional, post-transcriptional and translational dysregulation occurring in a highly tissue-specific fashion. Affymetrix Human Exon 1.0ST microarray analysis was performed on 29 skeletal muscle samples and Fibroblast cell lines from mitochondrial disease patients and age- and gender-matched controls.

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Genome-wide Ifh1p occupancy at the OX growth phase and RC quiescent phase of the yeast metabolic cycle

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