What Is Epigenetics?

Science 29 October 2010: Vol. 330. no. 6004, p. 611 DOI: 10.1126/science.330.6004.611

INTRODUCTION TO SPECIAL ISSUE

INTRODUCTION:

What Is Epigenetics?

Guy Riddihough and Laura M. Zahn

The cells in a multicellular organism have nominally identical DNA sequences (and therefore the same genetic instruction sets), yet maintain different terminal phenotypes. This nongenetic cellular memory, which records developmental and environmental cues (and alternative cell states in unicellular organisms), is the basis of epi-(above)–genetics.

The lack of identified genetic determinants that fully explain the heritability of complex traits, and the inability to pinpoint causative genetic effects in some complex diseases, suggest possible epigenetic explanations for this missing information. This growing interest, along with the desire to understand the"deprogramming" of differentiated cells into pluripotent/totipotent states, has led to "epigenetic" becoming shorthand for many regulatory systems involving DNA methylation, histone modification,nucleosome location, or noncoding RNA. This is to be encouraged, but the labeling of nongenetic systems as epigenetic by default has the potential to confuse (see the related video atwww.sciencemag.org/special/epigenetics/).

So what is epigenetics? An epigenetic system should be heritable, self-perpetuating, and reversible (Bonasio et al., p. 612). Whether histone modifications (and many noncoding RNAs) are epigenetic is debated; it is likely that relatively few of these modifications or RNAs will be self-perpetuating and inherited. Looking beyond DNA-associated molecules, prions (infectious proteins) are clearly epigenetic, perpetuating themselves through altered folding states. These states can act as sensors of environmentalstress and, through the phenotypic changes they promote, potentially drive evolution (Halfmann and Lindquist, p.629).