Metabolic choreography of gene expression: nutrient transactions with the epigenome
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Review Metabolic choreography of gene expression: nutrient transactions with the epigenome BABUKRISHNA MANIYADATH, U S SANDRA and ULLAS KOLTHUR-SEETHARAM* Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India *Corresponding author (Email, [email protected], [email protected])
Eukaryotic complexity and thus their ability to respond to diverse cues are largely driven by varying expression of gene products, qualitatively and quantitatively. Protein adducts in the form of post-translational modifications, most of which are derived from metabolic intermediates, allow fine tuning of gene expression at multiple levels. With the advent of high-throughput and high-resolution mapping technologies there has been an explosion in terms of the kind of modifications on chromatin and other factors that govern gene expression. Moreover, even the classical notion of acetylation and methylation dependent regulation of transcription is now known to be intrinsically coupled to biochemical pathways, which were otherwise regarded as ‘mundane’. Here we have not only reviewed some of the recent literature but also have highlighted the dependence of gene regulatory mechanisms on metabolic inputs, both direct and indirect. We have also tried to bring forth some of the open questions, and how our understanding of gene expression has changed dramatically over the last few years, which has largely become metabolism centric. Finally, metabolic regulation of epigenome and gene expression has gained much traction due to the increased incidence of lifestyle and age-related diseases. Keywords. AMPK; chromatin; epigenetics; epitranscriptome; gene expression; metabolism; mitochondria; RNA; Sirtuins; TOR
1. Introduction Phenotypic variations and onset/progression of diseases have been associated with alterations in gene expression, either causally or consequentially. While genetic polymorphisms and/or mutations are major determinants, the contributions by modifications on DNA/RNA and of proteins that bind them, have emerged as key. Since many articles in this special issue have elaborated on chromatin, we have highlighted the interplay between gene expression and metabolism, which is bidirectional and is elicited at multiple levels. Environmental inputs have a huge impact on gene expression and is best exemplified by phenotypic dif-
This article is part of the Topical Collection: Chromatin Biology and Epigenetics. http://www.ias.ac.in/jbiosci
ferences in isogenic strains or monozygotic twins who are otherwise genetically identical. While dietary alterations are considered as one such input, emerging literature has established that most of the modifications that we have come to appreciate (on cellular proteins and specifically of chromatin) are derived from metabolic intermediates (Gut and Verdin 2013). Moreover epigenomic alterations are also associated with onset of diseases and aging within an individual (Maniyadath et al. 2018; Sen et al. 2
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