Custom Oligonucleotide Synthesis

Epigenetics

Epigenetics is the study of heritable traits that do not involve changes to their underlying DNA sequence. Epigenetic signals within the cell modulate particular transcriptional states (epigenetic states) necessary for the cell to “remember” previous stimulus events, including developmental signals and environmental changes (1). The molecular foundation of epigenetic signalling is the remodeling of chromatin, which occurs through a combination of (a) post-translational modification of amino acids in histone proteins, and (b) DNA methylation. The interplay between chromatin remodeling and other signaling molecules such as transcription factors and non-coding RNA controls the level and pattern of transcription from chromatin necessary to generate a given epigenetic state in the cell (2). The classic examples of epigenetic processes are cellular differentiation and maintenance of cell identity through multiple cell divisions over the lifetime of a multi-cellular organism (3). Epigenetic signals can be divided into two main categories, cis- and trans-. Trans-epigenetic states are primarily self-propagating transcriptional states maintained via feedback loops and transcription factor (TF) networks (4). For example, if an external stimulus causes a TF to activate its own transcription, the result is a (trans) epigenetic state that becomes self-sustaining when the stimulus is removed, and continues after cell division. Small RNAs (sRNAs) also sometimes function as trans-epigenetic signals (5). Trans-epigenetic states are often found in prokaryotes and single-celled eukaryotes, where they support cellular memory. Cis-epigenetic signals, by contrast, are actually physically associated, and inherited, with the particular chromosome upon which they act. Covalent modification of histones (the protein part of chromatin) and DNA methylation (typically by the conversion of deoxycytosine (dC) to 5-methyl-dC by various DNA methyltransferase enzymes) are key examples of cis-epigenetic signaling processes (6). For example, whenever two identical DNA sequences in the same cell are differentially regulated, they are under the control of a cis-epigenetic process. Genomic imprinting (the specific expression of either the maternal or paternal gene in a cell) and X-chromosome inactivation in mammals are both cis-epigenetic phenomenon (7).
References 1. Bonasio, R., Shengjiang, T., Reinberg, D. “Molecular Signals of Epigenetic States”. Science (2010), 330: 612-616. 2. Jablonka, E., Lamb, M.J., Lachmann, M. “Evidence, mechanisms and models for the inheritance of acquired characteristics”. J. Theoret. Biol. (1992), 158: 245-268. 3. Ringrose, L., Paro, R. “Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins”. Ann. Rev. Genet. (2004), 38: 413-443. 4. Alon, U. An Introduction to Systems Biology: Design Principles of Biological Circuits. Chapman & Hall/CRC Press/Taylor & Francis, Boca Raton, FL, 2006. 5. Moazed, D. “Small RNAs in transcriptional gene silencing and genome defense”. Nature (2009), 457: 413-420. 6. Talbert, P.B., Henikoff, S. “Histone variants—ancient wrap artists of the epigenome”. Nat. Rev. Mol. Cell. Biol. (2010), 11: 264-275. 7. Allis, C.D., Jenuwein, T., Reinberg, D. “Epigenetics”, M. Caparros, Ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. ed 1, 2007.