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Introduction to the special issue of Neurobiology of Learning and Memory on epigenetics and memory
Neurobiology of Learning and Memory 96 (2011) 1
Contents lists available at ScienceDirect
Neurobiology of Learning and Memory journal homepage: www.elsevier.com/locate/ynlme
Editorial
Introduction to the special issue of Neurobiology of Learning and Memory on epigenetics and memory This special issue is devoted to capturing the current understanding of the role of epigenetic mechanisms involved in learning and memory. All papers were peer-reviewed and revised prior to publication. Although the concepts behind epigenetics (the term is defined below) have been with us for over half a century, how they may be applied to the understanding of the neurobiology of learning and memory is relatively new. This special issue represents the first time that investigators examining the role of epigenetic mechanisms in memory have come together to give their opinion, criticism, and speculation on this rapidly moving field. The contributing authors were encouraged to speculate on what is unique about the involvement of epigenetic mechanisms in memory and what that may mean with respect to human cognitive disorders and novel therapeutic approaches as well. This has resulted in reviews that are exciting and provide a glimpse over the horizon. Defining the term epigenetics The term epigenetics was coined by Conrad Hal Waddington (1905–1975) in 1942 to define the mechanisms by which ‘‘the genes of the genotype bring about phenotypic effects’’. He referred to the epigenotype or the epigenetic landscape as a way to help think about how gene expression regulates development. In 1958, in an article entitled ‘Epigenetic control systems,’ Nanney (1958) discussed that the advances in chemical genetics and emerging agreement regarding the structure and function of primary genetic material revealed a more clear distinction between two types of cellular control systems. One control system is dependent on primary genetic material. The other control system represents ‘‘auxiliary mechanisms with different principles of operation involved in determining which specificities are to be expressed in any particular cell.’’ These two systems were described by Nanney (1958) as a genetic system and an epigenetic system, in which the term epigenetics ‘‘is chosen to emphasize the reliance of this system on the genetic system.’’ This helped explain how cells with the same genotype could have different phenotypes that were heritable and persisted for numerous generations (cellular memory). A commonly accepted current definition of epigenetics is: ‘‘An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence’’ (Berger, Kouzarides, Shiekhattar, & Shilatifard, 2009). A similar definition is given in the book ‘Epigenetics’ by Allis, Jenuw-
1074-7427/$ - see front matter Ó 2011 Published by Elsevier Inc. doi:10.1016/j.nlm.2011.04.013
ein, Reinberg, and Caparros (2007). Although in the same book one can find a more general definition of epigenetics that does not involve the term heritable: ‘‘Epigenetics can be defined as changes in gene transcription through modulation of chromatin, which is not brought about by changes in DNA sequence.’’ As neurons are postmitotic cells, this later definition (absent of the term heritable) is favored among neuroscientists, especially in the field of learning and memory. This definition will be employed throughout this issue of NLM. Obviously, it is crucial to understand where these definitions come from (Haig 2004), and how they are used by researchers in different disciplines, as they carry certain baggage. For example, epigenetics has been used to refer to a mechanism by which ‘stable’ gene expression profiles are maintained for specific cellular functions. This can be misleading because it suggests a rigidity that contradicts the view of neuronal plasticity inherent to learning and memory. Although epigenetic mechanisms may be involved in the regulation of gene expression profiles, and may indeed contribute to stable changes in gene expression or maintaining altered cellular states, it should be kept in mind that these mechanisms are highly dynamic. The idea that we can manipulate epigenetic mechanisms brings tremendous excitement and promise with regard to basic understanding of molecular mechanisms underlying learning and memory, but as important, to a new avenue of diagnosis, prognosis, and treatment for human cognitive disorders and diseases. References Allis, C. D., Jenuwein, T., Reinberg, D., & Caparros, M. L. (2007). Epigenetics (1st ed.). Cold Spring Harbor Laboratory Press. Berger, S. L., Kouzarides, T., Shiekhattar, R., & Shilatifard, A. (2009). An operational definition of epigenetics. Genes and Development, 23, 781–783. Haig, D. (2004). The (dual) origin of epigenetics. Cold Spring Harbor Symposia on Quantitative Biology, 69, 67–70. Nanney, D. L. (1958). Epigenetic control systems. Proceedings of the National Academy of Science, 44, 712. Waddington, C. (1942). The epigenotype. Endeavour, 1, 18.
Associate Professor Marcelo Wood University of California Irvine, Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, United States E-mail address: [email protected]
Contents lists available at ScienceDirect
Neurobiology of Learning and Memory journal homepage: www.elsevier.com/locate/ynlme
Editorial
Introduction to the special issue of Neurobiology of Learning and Memory on epigenetics and memory This special issue is devoted to capturing the current understanding of the role of epigenetic mechanisms involved in learning and memory. All papers were peer-reviewed and revised prior to publication. Although the concepts behind epigenetics (the term is defined below) have been with us for over half a century, how they may be applied to the understanding of the neurobiology of learning and memory is relatively new. This special issue represents the first time that investigators examining the role of epigenetic mechanisms in memory have come together to give their opinion, criticism, and speculation on this rapidly moving field. The contributing authors were encouraged to speculate on what is unique about the involvement of epigenetic mechanisms in memory and what that may mean with respect to human cognitive disorders and novel therapeutic approaches as well. This has resulted in reviews that are exciting and provide a glimpse over the horizon. Defining the term epigenetics The term epigenetics was coined by Conrad Hal Waddington (1905–1975) in 1942 to define the mechanisms by which ‘‘the genes of the genotype bring about phenotypic effects’’. He referred to the epigenotype or the epigenetic landscape as a way to help think about how gene expression regulates development. In 1958, in an article entitled ‘Epigenetic control systems,’ Nanney (1958) discussed that the advances in chemical genetics and emerging agreement regarding the structure and function of primary genetic material revealed a more clear distinction between two types of cellular control systems. One control system is dependent on primary genetic material. The other control system represents ‘‘auxiliary mechanisms with different principles of operation involved in determining which specificities are to be expressed in any particular cell.’’ These two systems were described by Nanney (1958) as a genetic system and an epigenetic system, in which the term epigenetics ‘‘is chosen to emphasize the reliance of this system on the genetic system.’’ This helped explain how cells with the same genotype could have different phenotypes that were heritable and persisted for numerous generations (cellular memory). A commonly accepted current definition of epigenetics is: ‘‘An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence’’ (Berger, Kouzarides, Shiekhattar, & Shilatifard, 2009). A similar definition is given in the book ‘Epigenetics’ by Allis, Jenuw-
1074-7427/$ - see front matter Ó 2011 Published by Elsevier Inc. doi:10.1016/j.nlm.2011.04.013
ein, Reinberg, and Caparros (2007). Although in the same book one can find a more general definition of epigenetics that does not involve the term heritable: ‘‘Epigenetics can be defined as changes in gene transcription through modulation of chromatin, which is not brought about by changes in DNA sequence.’’ As neurons are postmitotic cells, this later definition (absent of the term heritable) is favored among neuroscientists, especially in the field of learning and memory. This definition will be employed throughout this issue of NLM. Obviously, it is crucial to understand where these definitions come from (Haig 2004), and how they are used by researchers in different disciplines, as they carry certain baggage. For example, epigenetics has been used to refer to a mechanism by which ‘stable’ gene expression profiles are maintained for specific cellular functions. This can be misleading because it suggests a rigidity that contradicts the view of neuronal plasticity inherent to learning and memory. Although epigenetic mechanisms may be involved in the regulation of gene expression profiles, and may indeed contribute to stable changes in gene expression or maintaining altered cellular states, it should be kept in mind that these mechanisms are highly dynamic. The idea that we can manipulate epigenetic mechanisms brings tremendous excitement and promise with regard to basic understanding of molecular mechanisms underlying learning and memory, but as important, to a new avenue of diagnosis, prognosis, and treatment for human cognitive disorders and diseases. References Allis, C. D., Jenuwein, T., Reinberg, D., & Caparros, M. L. (2007). Epigenetics (1st ed.). Cold Spring Harbor Laboratory Press. Berger, S. L., Kouzarides, T., Shiekhattar, R., & Shilatifard, A. (2009). An operational definition of epigenetics. Genes and Development, 23, 781–783. Haig, D. (2004). The (dual) origin of epigenetics. Cold Spring Harbor Symposia on Quantitative Biology, 69, 67–70. Nanney, D. L. (1958). Epigenetic control systems. Proceedings of the National Academy of Science, 44, 712. Waddington, C. (1942). The epigenotype. Endeavour, 1, 18.
Associate Professor Marcelo Wood University of California Irvine, Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, United States E-mail address: [email protected]