Preface

Epigenetic changes are heritable and reversible modifications that significantly affect gene expression without any change in DNA sequence. Epigenetic mechanisms include DNA methylation, imprinting, chromatin remodelling via histone modifications, and the production of specific non-coding RNA. The epigenetic signature is remodelled during the lifespan as a direct consequence of both environment and lifestyle. Therefore, health or disease status strongly depends on epigenetic marks. In addition, the epigenetic signature of gametes and parental experience may cause transgenerational epigenetic inheritance, thus affecting offspring health. Lastly, emerging evidence reveals that epigenetic marks, and in particular circulating non-coding RNAs, represent upcoming biomarkers for the prevention, diagnosis and treatment of diseases.

This book summarizes the current knowledge in the field of epigenetics in five chapters. Chapter 1 provides a brief introduction to epigenetics and is followed by a study on epigenetics in plants (Chapter 2) and three chapters concerning epigenetics in health and disease: cancer (Chapter 3), the photoperiodic system (Chapter 4) and aging (Chapter 5).

Chapter 2 by Drs. Singroha and Sharma describes the epigenetic regulation of the plant genome, focusing on the epigenetic modifications in plants under abiotic stress.

Environmental factors and lifestyle both affect epigenetic marks. Thus, Chapter 3 by Dr. Tobias et al. analyses the role of microRNAs in cancer and cachexia, pointing out the possible contribution of physical activity to tumor regression.

Chapter 4 by Dr. Haim et al. describes the consequences of artificial light at night and the links between chasing darkness away and epigenetic modifications.

Lastly, Chapter 5 by Dr. Mutirangura presents an interesting hypothesis for aging based on genome-wide hypomethylation. Such a condition may cause genomic instability and aging-associated disease phenotypes, thus explaining how the DNA of elderly people is prone to damage.

Taken together, the chapters in this book target a wide audience of basic and clinical scientists, teachers and students interested in gaining a better understanding of epigenetics.

> **Rosaria Meccariello** University of Naples Parthenope, Italy

**1**

**Chapter 1**

**1. Definition**

in Summary

nucleotide sequence of DNA [3].

**2. Molecular mechanisms**

ing RNA (ncRNA) [4, 5].

gene silencing.

*Rosaria Meccariello*

Introductory Chapter: Epigenetics

In 1940 the developmental biologist Conrad H. Waddington firstly used the term "epigenetics" to describe "*the interaction of genes with their environment, which bring the phenotype into being*" [1]. Two years later, Conrad Waddington pointed out that "*It is possible that an adaptive response can be fixed without waiting for the occurrence of a mutation*" [2]. Thus, epigenetic modifications are heritable and reversible modifications that significantly affect gene expression without any change in the

Classically, epigenetic mechanisms include (i) the methylation of DNA, (ii) the imprinting, (iii) the remodeling of chromatin, and (iv) the production of noncod-

Genomic imprinting is a DNA methylation-dependent phenomenon, occurring

Nuclear DNA is structured in chromatin, an instructive DNA scaffold that can respond to external cues regulating DNA activity, composed of histone and nonhistone proteins [9]. Euchromatin, which is the transcriptionally active region of the DNA, represents the loosely folded part of the chromatin; heterochromatin, which is a transcriptionally poorly active region of the DNA, represents the tightly folded part of the chromatin [10]. Therefore, the transcription rate of genes is strongly affected by dynamic chromatin remodeling. In this respect, posttranslational modifications of histone tails like methylation and acetylation play critical roles, by affecting either the affinity of transcriptional factors for gene promoter region or the recruitment to chromatin of nonhistone protein, thus disturbing chromatin contacts [10]. Histone tail acetylation usually promotes the transcription and is a feature of euchromatin; by contrast, histone tail methylation has usually an inhibi-

during embryogenesis; it causes genes to be expressed from a parent of origin-

specific manner [8] and specifically interests at some genetic loci.

tory role for transcription and is a feature of heterochromatin.

The family of ncRNA includes a large set of RNAs like the well-known microRNA (miRNA) or the less known long noncoding RNA (lnRNA) and tRNA fragments (tRF) among others [11]. NcRNAs are involved in the control of gene expression and in the regulation of many biological functions in several tissues;

The methylation of DNA usually occurs at the 5-position of DNA cytosine (5mC) in the CpG islands located within the promoter region of specific genes; such a modification inhibits both the binding of transcription factors to DNA and affects the recruitment of proteins involved in chromatin remodeling [6, 7], thus causing

## **Chapter 1**
