When histones are under glucose starvation
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Mini-Review When histones are under glucose starvation JAEHYOUN LEE1, SEUNGHEE OH1, SUSAN M ABMAYR1,2 and JERRY L WORKMAN1* 1 2
Stowers Institute for Medical Research, Kansas City, MO 64110, USA
Department of Anatomy and Cell Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA *Corresponding author (Email, [email protected])
Under nutritional stress, cells undergo metabolic rewiring that results in changes of various cellular processes that include gene transcription. This transcriptional regulation requires dynamic chromatin remodeling that involves histone post-translational modifications. There are several histone marks that may act as switches upon starvation for stress-response pathways. Keywords. response
AMPK; histone modification; histone PTMs; metabolic rewiring; nutritional stress; stress-
1. Introduction Nutritional stress is a common event for most organisms. Upon stress, cells undergo metabolic rewiring to adapt to the new environmental conditions and to promote cell survival. This metabolic reprogramming incurs a massive change of various cellular processes that include gene transcription. This transcriptional regulation requires extensive chromatin remodeling as DNA is packed with histones into repressive nucleosome structures. These dynamic chromatin structure changes involve various post-translational modifications (PTMs) of histones that alter their interactions with other proteins as well as the innate interaction between DNA and histones. Indeed, many reports now describe histone post-translational modifications that change under conditions of nutritional stress and correlate with specific transcription changes that maintain cellular energy homeostasis. In this review, we focus on histone marks that may serve as switches to turn on stress-response pathways upon glucose starvation.
This article is part of the Topical Collection: Chromatin Biology and Epigenetics. http://www.ias.ac.in/jbiosci
2. AMPK as the core regulator of global histone modification Adenosine 50 monophosphate-activated protein kinase (AMPK) functions as the key modulator for responses that occur upon nutritional stress (reviewed in Herzig and Shaw 2018). AMPK phosphorylates many transcription factors including PGC-1a, FOXO family proteins, and CREB, which are all involved in induction of the stress response (Canto´ and Auwerx 2010). As reviewed recently by Gongol et al. (2018), AMPK can affect various global histone PTMs. It regulates global histone acetylation by increasing the available acetyl coenzyme A (acetyl-CoA) pool. Upon glucose deprivation, AMPK phosphorylates serine 659 of acetyl-CoA synthetase short-chain family member 2 (ACSS2), which converts acetate to acetyl-CoA. ACSS2 S659 phosphorylation then leads to nuclear localization of ACSS2, producing nuclear acetyl-CoA for histone acetyltransferases (HATs) (Li et al. 2017). AMPK increases acetyl-CoA indirectly by an inhibitory phosphorylation of acetyl-CoA carboxylase (ACC
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