RT Journal Article
SR Electronic
T1 The INO80 Chromatin Remodeler Sustains Metabolic Stability by Promoting TOR Signaling and Regulating Histone Acetylation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 184440
DO 10.1101/184440
A1 Sean L. Beckwith
A1 Erin K. Schwartz
A1 Pablo E. Garcia-Nieto
A1 Devin A. King
A1 Graeme J. Gowans
A1 Ka Man Wong
A1 Wei Yao
A1 Tessa L. Eckley
A1 Alexander P. Paraschuk
A1 Egan Peltan
A1 Laura R. Lee
A1 Ashby J. Morrison
YR 2017
UL http://biorxiv.org/content/early/2017/09/04/184440.abstract
AB 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, including mitochondrial maintenance. INO80 is also needed to communicate TORC1-mediated signaling to chromatin and maintains histone acetylation at TORC1-responsive genes. Furthermore, computational 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.