Contents

### **Preface XI**



Chapter 9 **Cytosine Modifications and Distinct Functions of TET1 on Tumorigenesis 187 <sup>X</sup>** Contents Preface

Cuili Ma, Pengfei Ji, Nina Xie and Yujing Li

Chapter 10 **Role of COX-2 Promoter Methylation and Helicobacter pylori Infection in Impaired Gastric Ulcer Healing 207** Hiroshi Yasuda, Yoshiyuki Watanabe, Ritsuko Oikawa and Fumio Itoh

Since Charles Darwin put forward his famous bottom-up theory of natural selection in "The Origin of Species" in 1859, genetics and nowadays genomics increasingly gained world-wide attention [1]. The frequently debated cartoons depicting the descent of man from apes mark the transition from ancient mystical beliefs to a scientifically falsifiable modern theory of the origin of life and mankind. Jean-Baptiste Lamarck had already put forward a top-down hypothesis in 1809 in his famous book "Philosophie Zoologique" symbolized by the elongating giraffe-neck longing for leaves at tree-tops [2]. It achieved public attention due to the 'motivated change' paradigm that remains simple to grasp, actually to this day. The discovery of the DNA double helix and the four base code culminated in the publicly much anticipated race to decipher the sequence of the human genome in 2002 by the public Human Genome Project and the private initiative of Craig Venter. Now everything would be known about humans, their lives from birth to death as well as all species, the origin of life and its future - so resounded the promise of some and the happy

But are 3 billion A, T, G, C bases and the ensuing code for ~20,000 proteins really sufficient explanation for the holy grail of human life, as would be suggested by monozygotic twin physiologic and physiognomic identity? Or is the real situation much more complex, potentially involving a multitude of interactions of the genotype ranging from its own internal physicochemical foundation, via the phenotype it is creating, up to the entire ecosystem, which is itself made up of many genomes? There is little doubt that a purely reductionistic approach cannot explore the full extent of the interaction-networks of genomes. While reductionism can formally identify biological variables that are rate-limiting *under* the experimental conditions that are tested, there may always be biological signals that are not observed

Since the initial investigations in the late 18th century much progress has been made, achieving a picture of the notoriously hard-to-access eukaryotic cell nucleus and the chromatin it contains [3]. This revealed a layered organization of the physical genome comprising DNA, nucleosomes, chromatin quasi-fibres, chromatin loops, loop aggregates/rosettes, as well as chromosome arms, entire chromosomes, and their position within the cell nucleus as outlined in Chapter 4 of this book.

Intriguingly, it also has become apparent relatively early already that there are heritable phenotype changes that do not involve alterations in the nucleotide sequence. This led to the concept of epigenetic coding initially introduced by Conrad Hall Waddington in 1942 [4] to explain why almost every cell of an organism harbours the same DNA but does not express the same parts of the genetic information, enabling cell fate determination and cell lineage differentiation to yield all the cells

This book addresses current issues in the fields of epigenetics and chromatin ranging from more theoretical overviews in the first four chapters to much more detailed methodologies and insights into diagnostics and treatments in the other chapters.

because they were not solicited during the experiment.

of an organism, as explained in Chapter 1.

belief of many.

