Abstract
Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct functional subunit modules. We identified a strikingly divergent genetic signature for the Ies6 subunit module that links the INO80 complex to metabolic homeostasis. In particular, mitochondrial maintenance is disrupted in ies6 mutants. INO80 is also needed to communicate TORC1-mediated signaling to chromatin, as ino80 mutants exhibit defective transcriptional profiles and altered histone acetylation of TORC1-responsive genes. Furthermore, comparative analysis reveals subunits of INO80 and mTORC1 have high co-occurrence of alterations in human cancers. Collectively, these results demonstrate that the INO80 complex is a central component of metabolic homeostasis that influences histone acetylation and may contribute to disease when disrupted.
Highlights
Chromatin is a complex structure that is dynamically reorganized to facilitate DNA-templated processes such as transcription, chromosome segregation, DNA replication and DNA repair
One of the key ways that cells regulate their metabolism is through changes in metabolic gene expression
We performed an extensive genetic screen in the budding yeast Saccharomyces cerevisiae in order to identify chromatin regulators of cellular metabolism
Summary
Chromatin is a complex structure that is dynamically reorganized to facilitate DNA-templated processes such as transcription, chromosome segregation, DNA replication and DNA repair. Different subunits of the evolutionarily conserved INO80 chromatin remodeling complex have demonstrated roles in diverse processes, such as transcription [5,6,7], replication [8,9,10], DNA damage responses [11,12,13,14], telomere regulation [15], mitotic stability [16,17], and metabolic homeostasis [18]. These studies exemplify the functional diversity of the INO80 complex in different pathways [19,20,21], and suggest the partitioning of diverse functions among the subunits of the INO80 complex
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
