Epigenetics

Epigenetics can be defined as acquired changes in chromatin structure that arise independently of a change in the underlying DNA nucleotide sequence. Epigenetic modifications - including acetylation, methylation, phosphorylation, and ubiquitination amongst others - alter the accessibility of DNA to transcription machinery and therefore influence gene expression. Ongoing research is revealing the extent of the influence of epigenetics in disease states, and continues to provide a wealth of novel therapeutic targets.

Targets
Literature
Molecular Machinery

Epigenetic mechanisms integrate environmental changes at the cellular level and enable cellular plasticity. As a result, they are involved in pathologies related to diet, lifestyle and environmental exposure to toxins, including cancer, inflammation and metabolic disorders. Proteins that carry out these epigenetic modifications can be thought of as being either "writers", "readers" or "erasers".

Epigenetic Writers »

Epigenetic writers catalyze the addition of chemical groups onto either histone tails or the DNA itself. These modifications are known as epigenetic marks. More Information »

Epigenetic Readers »

Epigenetic reader domains can be thought of as effector proteins that recognize and are recruited to specific epigenetic marks. "Writer" and "eraser" enzymes may also contain such reader domains, leading to the coordination of "read-write" or "read-erase" mechanisms. More Information »

Epigenetic Erasers »

Epigenetic marks are not necessarily permanent modifications; instead, they can be removed by a group of enzymes known as "erasers" in order to reverse the influence of a given epigenetic mark on gene expression. More Information »

Literature for Epigenetics

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

  • Hypertension
  • Thrombosis and Hemostasis
  • Atherosclerosis
  • Myocardial Infarction
  • Ischemia/Reperfusion Injury
  • Arrhythmias
  • Heart Failure
Epigenetics

Epigenetics Scientific Review

Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.

Epigenetics

Epigenetics Research Bulletin

Produced by Tocris and updated in 2014, the epigenetics research bulletin gives an introduction into mechanisms of epigenetic regulation, and highlights key Tocris products for epigenetics targets including:

  • Bromodomains
  • DNA Methyltransferases
  • Histone Deacetylases
  • Histone Demethylases
  • Histone Methyltransferases
Cell Cycle & DNA Damage Repair

Cell Cycle & DNA Damage Repair Poster

In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.

Epigenetics in Cancer

Epigenetics in Cancer Poster

Adapted from the 2015 Cancer Product Guide Edition 3, this poster summarizes the main epigenetic targets in cancer. The dysregulation of epigenetic modifications has been shown to result in oncogenesis and cancer progression. Unlike genetic mutations, epigenetic alterations are considered to be reversible and thus make promising therapeutic targets.

Rheumatoid Arthritis

Rheumatoid Arthritis Poster

Rheumatoid arthritis (RA) is a chronic destructive inflammatory autoimmune disease that results from a breakdown in immune tolerance, for reasons that are as yet unknown. This poster summarizes the pathology of RA and the inflammatory processes involved, as well as describing some of the epigenetic modifications associated with the disease and the potential for targeting these changes in the discovery of new treatments.

Epigenetics: Molecular Machinery

Epigenetic Mechanism "Writer" Enzymes "Reader" Domains "Eraser" Enzymes
DNA Methylation DNA Methyltransferases Methyl-CpG Binding Domains Active DNA Demethylation Enzymes; Passive DNA Demethylation
Histone Acetylation Histone Acetyltransferases Bromodomains; Tandem PHD Fingers; Pleckstrin Homology Domains Histone Deacetylases
Histone Arginine Methylation Protein Arginine Methyltransferases (PRMTs) Tudor Domains (recognize symmetrically dimethylated arginines); WD40 Domains Histone Demethylases (JMJD6); Peptidyl Arginine Deiminases (putative)
Histone Lysine Methylation Histone Lysine Methyltransferases Chromodomains; Tudor Domains; PHD Fingers; MBT Domains; ZF-CW Proteins; WD40 Domains; PWWP Histone Lysine Demethylases
Histone Phosphorylation Kinases (JAK2, ATM/ATR, PKC, PKA, Haspin, Aurora B Kinase, RSK2, AMPK, MSK, MEK) Chromoshadow Domains (phosphoTyrosine); 14.3.3 Proteins (phosphoSerine); BIR Domains; BRCT Proteins Protein Serine/Threonine Phosphatases; Protein Tyrosine Phosphatases
Histone Ubiquitination Ubiquitin E2 Conjugases; Ubiquitin E3 Ligases Unknown Deubiquitinating Enzymes

Acronyms

AMPK - Adenosine monophosphate-activated kinase; ATM - Ataxia telangiectasia mutated; ATR - Ataxia telangiectasia and RAD3 related; BIR - Baculovirus inhibitor of apoptosis protein repeat; BRCT - Breast cancer type 1 susceptibility protein C terminus; JAK2 - Janus kinase 2; JMJD6 - Jumonji domain-containing 6 protein; MBT - Malignant brain tumor; MEK - Mitogen-activated protein kinase kinase; MSK - Mitogen- and stress-activated kinase; PHD - Plant homeodomain; PKA - Protein kinase A; PKC - Protein kinase C; PWWP - Proline-Tryptophan-Tryptophan-Proline; RSK2 - Ribosomal S6 kinase C; ZF-CW - Zinc Finger CW