Inheritance of Stress-Induced, ATF-2-Dependent Epigenetic Change

Abstract

Atf1, the fission yeast homolog of activation transcription factor-2 (ATF-2), contributes to heterochromatin formation. However, the role of ATF-2 in chromatin assembly in higher organisms remains unknown. This study reveals that Drosophila ATF-2 (dATF-2) is required for heterochromatin assembly, whereas the stress-induced phosphorylation of dATF-2, via Mekk1-p38, disrupts heterochromatin. The dATF-2 protein colocalized with HP1, not only on heterochromatin but also at specific loci in euchromatin. Heat shock or osmotic stress induced phosphorylation of dATF-2 and resulted in its release from heterochromatin. This heterochromatic disruption was an epigenetic event that was transmitted to the next generation in a non-Mendelian fashion. When embryos were exposed to heat stress over multiple generations, the defective chromatin state was maintained over multiple successive generations, though it gradually returned to the normal state. The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure.

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

“…Epigenetic inheritance has been demonstrated in several species including worm (2), fly (3) and mouse species (4,5). Epigenetic inheritance can be modulated by environmental factors and transmitted to subsequent generations via germline cells (6,7).…”

When is incomplete epigenetic resetting in germ cells favoured by natural selection?

“…Recent data from both animals and plants indicate that epigenetic resetting is not always complete and hence that acquired epigenetic states may be transmitted from parents to offspring ('germ-line epigenetic inheritance' or 'incomplete epigenetic resetting' or 'incomplete epigenetic reprogramming'; e.g. [6][7][8][9][10][11][12][13][14] reviewed in [4,5,[15][16][17][18][19]). …”

Genetics of germ cell development

“…140 In D. melanogaster, an osmotic or heat stress stimulus can disrupt the activity of the transcription factor ATF-2 and deposition of the repressive histone modification H3K9me2, and this disruption can be transmitted to the next generation in a non-Mendelian manner. 141 In mice, F1 offspring of males fed a low-protein diet exhibit altered liver gene expression profiles, and F1 female offspring of male rats fed a high-fat diet have impaired glucose tolerance and insulin secretion despite being indistinguishable by genotype. 142,143 One historical cohort study in humans has also suggested a transgenerational effect of paternal nutrition on the metabolic status of children and grandchildren.…”