Molecular bases of epigenetic mechanisms
2021
Ezequiel Lacunza
The most common definition of epigenetics is derived from its own term: "epi" (above, above, beyond) and "genetic" (DNA sequence), referring to a layer of information that exists beyond that encoded in the DNA sequence, thereby making the genome work distinctively in different types of cells. The definition encompasses all chromatin and DNA modifications and other transcriptional regulators that act in the context of chromatin. These epigenetic mechanisms, which include DNA methylation, histone modification and processes mediated by non-coding RNAs, establish a balance that regulates gene expression in order to canalize the identity of the different cell types. Its disruption can trigger various pathologies, such as cancer or diabetes. In this talk I will review the basic concepts of epigenetics. Its history, molecular aspects, study methodologies and its role in development and disease, with special emphasis on obesity and type 2 diabetes. I will begin with a definition of epigenetics and its historical context. The states of chromatin that are representative of gene activity, euchromatin and heterochromatin, will be described, as well as the mechanisms involved in chromatin stability, gene regulation, transcriptional silencing, and the reversibility of both DNA methylation and histone modifications. The concepts of ncRNA-mediated regulation will be introduced. I will describe how technological advances have enabled a high resolution in the study of the epigenome. The role of epigenetics in development and disease will also be discussed, and how genetic predisposition, aging, and various environmental factors, including diet and physical activity, interact with, and impact on, the human epigenome.
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