This annual review issue is dedicated to “Epigenetics” an emerging but fast growing field in the postgenomic era involving nonMendelian heritable changes in gene expression that are not mediated by alterations in Watson-Crick base-pairing of the DNA sequence (1,2). Conrad Waddington (1905–1975) coined the term “epigenetics” and defined it as “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being” (1,2). Both Darwin and Lamarck, the founders of evolutionary theory, predicted that “evolution may favor the development of self-guiding mechanisms, maximizing variability where and when it is most likely to yield positive changes while minimizing phenotypic variability when and where it is not needed” (1,2), supporting the general idea of nonrandom evolution. Epigenetic regulation mediates adaptation to the environment by the genome lending plasticity that translates into the presenting phenotype, particularly under “mismatched” environmental conditions (3).

Most investigations focus on demonstrating chemical modifications of the DNA sequence and/or the nuclear histone proteins that in turn alter the configuration of chromatin affecting its packaging and accessibility within the nucleus. The state of chromatin is critically important for the transcription of genes. Thus, heterochromatin signifies tightly wound chromatin impeding access of specific DNA sequences (cis-elements) by nuclear trans-activating proteins, a process that inhibits gene transcription. On the other hand, euchromatin is an active state, in which the loosely wound chromatin allows binding of the promoter region of genes by activating proteins resulting in active transcription. This simple concept, while serving as the ultimate process, is complicated by nuclear transport via the nuclear membrane pore or retention of critically important proteins, the complex nuclear arrangement of chromatin and proteins in a network creating loops and higher order structures, and recruitment of various enzymes and proteins to transcription initiation complexes, that are vital for either activating or repressing transcription (4,5), along with the newly evolving role for noncoding RNAs (6,7). The organization of chromatin in the nucleus allows the close proximity of the 5′- and 3′- ends of chromatin setting the stage for factors that mediate mRNA processing at the 3′-end to be involved in transcription at the 5′-end. Further, the approximation of chromosomes lends to the process of nonrandom translocation that determines a particular cellular phenotype (4,5). This self-organization of the nucleus is thought to be responsible for the formation of nucleoli either in the presence or absence of a scaffolding network consisting of lamin and/or actin filaments (4,5).

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD