A critical appraisal of clinical epigenetics
Bernhard Horsthemke
Abstract
Modern epigenetics emerged about 40 years ago. Since then, the field has rapidly grown. Unfortunately, this development has been accompanied by certain misconceptions and methodological shortcomings. A profound misconception is that chromatin modifications are a distinct layer of gene regulation that is directly responsive to the environment and potentially heritable between generations. This view ignores the fact that environmental factors affect gene expression mainly through signaling cascades and the activation or repression of transcription factors, which recruit chromatin regulators. The epigenome is mainly shaped by the DNA sequence and by transcription. Methodological shortcomings include the insufficient consideration of genetic variation and cell mixture distribution. Mis- and overinterpretation of epigenetic data foster genetic denialism ("We can control our genes") and epigenetic determinism ("You are what your parents ate"). These erroneous beliefs can be overcome by using precise definitions, by raising the awareness about methodological pitfalls and by returning to the basic facts in molecular and cellular biology.