RESUMO
BACKGROUND: The execution of many genetic programs, influenced by environmental conditions, is epigenetically controlled. Thus, small molecules of the intermediate metabolism being precursors of most of nutrition-deriving epigenetic modifications, sense the cell surrounding environment. METHODS: Here we describe histone H4K16 acetylation distribution in S. cerevisiae nhp6ab mutant, using ChIP-seq analysis; its transcription profile by RNA-seq and its metabolic features by studying the metabolome. We then intersected these three -omic approaches to unveil common crosspoints (if any). RESULTS: In the nhp6ab mutant, the glucose metabolism is switched to pathways leading to Acetyl-CoA synthesis. These enhanced pathways could lead to histone hyperacetylation altering RNA transcription, particularly of those metabolic genes that maintain high Acetyl-CoA availability. CONCLUSIONS: Thus, the absence of chromatin regulators like Nhp6 A and B, interferes with a regulative circular mechanism where histone modification, transcription and metabolism influence each other and contribute to clarify the more general phenomenon in which gene regulation feeds metabolic alterations on epigenetic basis. GENERAL SIGNIFICANCE: This study allowed us to identify, in these two factors, a common element of regulation in metabolism and chromatin acetylation state that could represent a powerful tool to find out relationships existing between metabolism and gene expression in more complex systems.
Assuntos
Cromatina/genética , Proteínas de Ligação a DNA/genética , Proteínas HMGN/genética , Metaboloma/genética , Proteínas de Saccharomyces cerevisiae/genética , Acetilcoenzima A/genética , Acetilação , Epigênese Genética/genética , Glucose/metabolismo , Histonas/genética , Processamento de Proteína Pós-Traducional/genética , RNA-Seq , Saccharomyces cerevisiae/genéticaRESUMO
Maintaining a stable and balanced histone pool is of paramount importance for genome stability and fine regulation of DNA replication and transcription. This involves a complex regulatory machinery, exploiting transcription factors as well as histone chaperones, chromatin remodelers and modifiers. The functional details of this machinery are as yet unclear. Previous studies report histone decrease in mammalian and yeast HMGB family mutants. In this study we find that Nhp6 proteins, the S. cerevisiae HMGB1 homologues, control histone gene expression by affecting nucleosome stability at regulative regions of the histone clusters. In addition, we observe that histone gene overexpression in the nhp6ab mutant is accompanied by downregulated translation, which in turn is responsible for the histone decrease phenotype. Our observations allow us to incorporate Nhp6 proteins into the large group of chromatin factors that tightly regulate histone gene expression.