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Environmental Impact on Epigenetic Histone Language

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Part of the Epigenetics and Human Health book series (EHH)

Abstract

The epigenome of a cell or organism consists of chemical instructions acting with and upon genetic information to dictate gene expression. Such information exists in the form of noncoding RNAs, 5′ modifications at the DNA base cytosine, and combinatorial posttranslational modifications (PTMs) on histones. In this chapter, we explore the idea of a histone language written within the combinatorial complexity of PTMs. Examples of cross talk between DNA methylation and histone PTMs are presented. Environmental factors such as drugs and diet have profound impact on epigenetic information. Enzyme-catalyzed chromatin modification requires co-substrates that are key intermediates from major metabolic pathways. Links between metabolism and epigenetic mechanisms are discussed. Lastly, we discuss targeting the epigenome as a new paradigm for drug development.

Keywords

  • Histone code
  • Histone language
  • Metabolism
  • Posttranslational modification
  • Methyltransferase
  • Acetyltransferase
  • Deacetylase
  • Drugs
  • Epigenetic
  • Epigenome

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Fig. 7.1
Fig. 7.2

Abbreviations

AceCS:

Acetyl-CoA synthetase

ACL:

ATP citrate lyase

ATRX:

Alpha-thalassemia X-linked mental retardation

BET:

Bromodomain and extra-terminal

BHC80:

BRAF-histone deacetylase complex 80

ChIP:

Chromatin immunoprecipitation

DNMT:

DNA methyltransferase

HAT/KAT:

Histone/lysine acetyltransferase

HDAC:

Histone deacetylase

HP1:

Heterochromatin protein 1

ING2:

Inhibitor of growth 2

LSD1:

Lysine-specific demethylase 1

NTDs:

Neural tube closure defects

NUP98:

Nucleoporin 98

PHD:

Plant homeodomain

PRC:

Polycomb repressive complex

PTM:

Posttranslational modification

RAG2:

Recombination activating gene 2

SAHA:

Suberoylanilide hydroxamic acid

SAM:

S-Adenosyl-L-methionine

SILAC:

Stable isotope labeling with amino acids in cell culture

TAF3:

TBP-associated factor 3

THF:

Tetrahydrofolate

TSA:

Trichostatin A

UHRF1:

Ubiquitin-like containing PHD and RING finger domains 1

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Acknowledgments

I wish to apologize to the authors of studies that we did not have space to include. The laboratory is funded by NIH grants GM065386 and GM059785. I thank Brittany Albaugh for generating Figs. 7.1 and 7.2, with contribution from Sam Oliver on Fig. 7.1. I thank Elise Wagner for making Table 7.1 and Kristin Dittenhafer-Reed for making Table 7.2.

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Denu, J.M. (2013). Environmental Impact on Epigenetic Histone Language. In: Jirtle, R., Tyson, F. (eds) Environmental Epigenomics in Health and Disease. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23380-7_7

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