Biological embedding of experience: A primer on epigenetics

Abstract

Biological embedding occurs when life experience alters biological processes to affect later life health and well-being. Although extensive correlative data exist supporting the notion that epigenetic mechanisms such as DNA methylation underlie biological embedding, causal data are lacking. We describe specific epigenetic mechanisms and their potential roles in the biological embedding of experience. We also consider the nuanced relationships between the genome, the epigenome, and gene expression. Our ability to connect biological embedding to the epigenetic landscape in its complexity is challenging and complicated by the influence of multiple factors. These include cell type, age, the timing of experience, sex, and DNA sequence. Recent advances in molecular profiling and epigenome editing, combined with the use of comparative animal and human longitudinal studies, should enable this field to transition from correlative to causal analyses.

Childhood Physical Neglect Is Associated With Exaggerated Systemic and Intracellular Inflammatory Responses to Repeated Psychosocial Stress in Adulthood

“…Although the present results are based on exposure to repeated acute stress within the context of a highly controlled lab environment, they have implications for the long-term health of those exposed to child maltreatment experiences in their youth. The biological embedding model (41,42) posits that early adversity programs cells of the innate immune system to respond to challenge in a pro-inflammatory fashion. Although likely adaptive in the short-term, the resulting more aggressive immune system response may result in a pro-inflammatory immune profile that confers a long-term increase in disease risk.…”

Critical period regulation across multiple timescales

“…Chromatin methylation patterns are also altered by neural activity (126), enabling early environmental changes to prime the system for future physiological and behavioral demands. Recent work reveals DNA methylation also occurs at non-CpG cytosines (127). Neurons preferentially methylate non-CpG cytosines (mCH) during postnatal development with a divergence of methylation patterns in cortex occurring by the third postnatal week to yield early differences in gene expression by subtype (128).…”

Functional testing of ASD-associated genes

“…Gene-Environment Interactions on Behavioral Phenotypes Are Pervasive. Genetic variation predisposes individuals to behave in a certain way, and the environment (which itself is multidimensional) can modify this predisposition (11,12). In model organisms, the modification of gene expression through experience can readily be seen at the molecular level acting through gene regulatory networks that act within circuits (13).…”