Genetics Week 2010 (December 13-16, 2010)

The UPLB Genetics Society

in celebration of its

27th Founding Anniversary

presents

Genetics Week 2011

(13-16 December)

"Uncovering Epigenetic Inheritance"

A BRIEF INTRODUCTION TO EPIGENETICS

Epigenetics refers to the study of heritable changes in gene expression that occur without a change in DNA sequence including DNA modification and chromosome remodelling. These changes may remain through succeeding cell division for the remainder of the cell's life and may last through generations.

18 January Issue of TIME

Program of Activities:

9 December

First BIO 30 Tutorials

Second Semester of A.Y. 2010-2011

14 December

Opening of the Exhibit

Week-long Rare Disease Signature Campaign

IQlympics Quiz Contest

15 December

Open Tambayan

Figure 1. Epigenetic Mechanisms and Health Endpoints

Short History

1942. The term "epigenetics" was coined by the developmental biologist Conrad Waddington. It was first defined as the interaction of genes with their environment which induce developmental phenotypes.

1953. James Watson and Francis Crick (1916- 2004) describe the structure of the DNA double helix in terms of the four letters of the genetic alphabet. DNA is recognized as the hereditary genetic material.

1975. Holiday and Pugh first proposed DNA Methylation - covalent chemical modifications on the DNA such as cytosine-gaunine (CpG) dinucleotide methylation.

1980s. Gene sequencing revolution begins.

1988. Elucidation of X-Chromosome Inactivation (Enables men and women to have equal expression of the genes carried on the X chromosome despite the fact that women have two X chromosome copies and men have only one. The inactive X chromosome is packaged into heterochromatin through methylation)

1990s. Discovery of histone modifcation and understanding the chromatin structure. Epigenetics was given its present-day definition.

2005. Epigenome mapping begins.

Mechanism of Epigenetic Modifications

Figure 2. Schematic of Epigenetic Modifications (Rodenhiser and Mann, 2006)

DNA Methylation

DNA Methylation occurs at the cytosine of CpG dinucleotides. Methylated cytosine (5mC) is often referred as the fifth base as it plays different roles in celluar function. DNA metylation inhibits transcription of the DNA as methylated cytosine inteferes with transcription factor binding proteins.

Chromatin Packaging

Chromatin is a nucleoprotein complex composed of an array of nucleosomes (linear DNA coiled into histone proteins) in its most compact form. The packaging of chromatin may be changed through post-translational modification of histone proteins, including histone acetylation, methylation, unbiquitinilation and phosphorylation.

Packaging of the chromatin is classified through two main chromatin states - heterochromatin and euchromatin.

• Heterochromatin refers to condensed or tightly bound conformation.
• Euchromatin refers to less condensed conformation leading to transcriptional activation.

Histone modifaction leads to either transcriptional activation and inactivation.

• Histone acetylation results to transcriptional activation since it decreases the affinity of histone proteins and DNA.
• Histone methlation at specific points may result to both activation and inactivation. Methylation of histone H3 at lysine 9 is associated with heterochromatin (inactive) and gene silencing while methylation of lysine 4 or 27 of the same histone leads to activation (euchromatin).

Significance

Genomic Imprinting and Human Disorders. Genomic imprinting is a form of gene regulation in which epigenetic chormosomal modifications drive differential gene expression in a parent-of-origin manner [1]. Imprinting is often called "gene memory" as the process allows genes to "remember" whether they are inherited from the mother or the father so that only the inherited paternal or maternal allele is expressed. Various pediatric disorders are associated with imprinting such as Prader-Willi Syndrome (genomic imprinting in chromosome 15q) and Bekcwith-Wiedemann Syndrome (abnormal maternal imprinting in chromosome 11).

Molecular Nutrition. Food micronutrients such as choline, Vitamin B12, folic acid and betaine are known to be as methyl donating substances. The importance of these micronutrients are highlighted during gestation in which epigenetic influences on gene expression may affect the offspring.

Treatment of Cancer. Epigenetic control of proto-onco genes and tumor supressor sequences suggest the possibility of applying epigenetics in cancer therapy as comformational changes in these genes directly affects the formation and progression of cancer. Development of this kind of treatment offers reversibility or normalization of cancer cells which is not offered by any other existing treatments.

Table 1. Methylation patterns of genes associated with various cancers. (Rodenhiser and Mann, 2006)

References:

[1] Dolinoy, D., J. Weidman and R. Jirtle. 2007. Epigenetic gene regulation: Linking early developmental environment to adult disease. Reproductive Toxicology 23: 297-307

[2] Rodenhiser D. and M. Mann. 2006.Epigenetics and human disease: translating basic biology into clinical applications. CMAJ 134(7):341-348.

Diagram: A scientific illustration of how epigenetic mechanisms can affect health. National Institutes of Health - US. [link]