Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity

An Epigenetics-Based, Lifestyle Medicine–Driven Approach to Stress Management for Primary Patient Care: Implications for Medical Education

“…88 These adaptations are thought to be carried out by epigenetic changes that alter fetal HPA axis development, 88,89 immune system function, 16,[90][91][92] and nervous system development. 91,92 Distress in pregnancy is also associated with defects in fetal cognitive development and subsequent childhood behavioral problems, exemplifying epigenetically modifiable relationships between prenatal stress and fetal phenotype outcomes. Fetal alcohol syndrome also has an epigenetic impact through DNA methylation of POMC (Proopiomelanocortin) neurons, which are regulators of HPA axis, immunity, and energy homeostasis, thus further exemplifying the relationship between perinatal stress and phenotype outcomes.…”

Stress Shaping Brains: Higher Order DNA/Chromosome Mechanisms Underlying Epigenetic Programming of the Brain Transcriptome

“…the brain chromosomal 'fragilome' which appears to underly certain aspects of neuroplasticity and memory storage and which appears to be closely linked with the stress hormonal system and immunoglobulin DNA strand break and genomic rearranging phenomena. The essential important characteristic of the brain fragilome is that of genetic breakage and recombination offering a structural basis for genetic/neuronal diversification and storage of memories (Gericke, 2010). Chromosomal fragile sites represent large heritable chromosomal regions that preferentially exhibit gaps or breaks after DNA synthesis is partially perturbed by stressors affecting the replication process (Arlt et al, 2006) and are classified as 'rare' or 'common', depending on their induction method and frequency within the population.…”

“…It is suggested that the abilities for diverse recognition of externally derived information, a dynamic response of somatic hypermutation followed by genome rearrangement creating a template for memory formation, and entry into a terminally differentiated state are features common to both the brain and immune system. Chromosome breaks and the various resulting structural rearrangements (genetic instability) have mostly been viewed in a pathological context by researchers, but controlled chromosomal breakage and rearrangement leading to altered gene expression without adverse effects may have been necessary for the evolutionary and neurodevelopmental flexibility required by the human brain (Gericke, 2010). Such chromosomal breakage relates to alterations in DNA higher order structures and studies of fragile sites at the level of chromosome organization reveal an unusual chromatin structure associated with fragile sites influencing formation of nucleosomes and the formation of nucleosome arrays (Wang, 2006).…”