Epigenetics – Blurring the Lines between Nature and Nurture


Epigenetics – the study of heritable phenotype changes that do not involve alterations in the DNA sequence, can have a significant impact on human health and disease susceptibility. In the last decade, this subject has attracted many interests, especially in complicated disorders such as behavior plasticity, memory, cancer, autoimmune disease, and addiction as well as neurodegenerative and psychological disorders.

Epigenetics most often involves changes that affect gene activity and expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal development. The standard definition of epigenetics requires these alterations to be heritable in the progeny of either cells or organisms. The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations, even though they do not involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently.

Some exciting advances in this field are in regard to the following:
i. The multifaceted roles of YY1 in the establishment of the cellular epigenetic landscape
ii. Setting up the epigenome through the histone methyltransferase SETDB1
iii. Sirtuin deacetylases in fungi – connecting metabolism to lifecycle progression, stress response, and genome stability
iv. Development-linked differences in cytosine 5-hydroxymethylation in mammalian DNA – relationship to 5-methylcytosine and function
v. The identification of mammalian proteins involved in epigenetics
vi. Chromatin-mediated response to stimuli
vii. The epigenetics of centromere function
viii. Dosage compensation in frogs and toads
ix. The diverse roles of long noncoding RNA in regulatory processes
x. Epigenetic mechanisms in Rett syndrome
xi. Facioscapulohumeral muscular dystrophy
xii. The epigenetics of nuclear reprogramming to pluripotency
xiii. Emerging role of the guanine-quadruplex DNA secondary structure in epigenetics
xiv. Clinical epigenetics in cancer – applications in diagnosis, prognosis and therapy
xv. Environment and the epigenetic transgenerational inheritance of disease
xvi. Metabolic inputs into epigenetics
xvii. Impact of environmental exposures on the epigenome

Recent new data and knowledge relating to the importance of epigenetics in different human disorders promise a vibrant future for epigenetics research. The new research will integrate high-throughput sequencing technologies and the sophisticated algorithms to analyze the large amount of data produced by sequenced epigenomes. The epigenomic data will provide a chance to discover new epigenetic marks and their functions in different types of tissues, early development, and disease states. The association of epigenetic marks with specific diseases can help the development of tools to diagnose patients and measure the severity of a disease. Although there are issues with specificity and efficacy of many drugs being tested in animal models, further research on the epigenetic mechanisms will surely help the development of better therapeutic pathways and agents in the near future.