A putative model attempting to depict different levels of genomic organization that may be associated with specific acquired spermatozoal defects. The sperm nucleus is broken down sequentially until the raw DNA. In human spermatozoa it is proposed that up to 15% of histone complexed DNA may remain after spermiogenesis while the remainder is all protamine complexed. For further information see Ward and Coffey (1991).
A dad’s food intake, drugs, exposure to toxic products and even stress can affect the development and health not only of his unborn children, but even of his grandchildren. They have discovered histones may play a crucial role in the process.
In the past, most epigenetics has focused on a process involving DNA and methyl groups that turn up or down the expression of specific genes.
The researchers were curious about whether histones might play a role in transmitting heritable information from fathers to their offspring because they are part of the content of sperm transmitted at fertilization. Although histones combine with DNA during cell formation, they act like a spool around which the DNA winds.
METHOD: They generated transgenic mice in which overexpression of the histone H3 lysine 4 (H3K4) demethylase LSD1/KDM1A during spermatogenesis reduced H3K4 dimethylation in sperm. KDM1A overexpression in one generation severely impaired development and survivability of offspring.
RESULTS: What they discovered was that there were dire consequences for the offspring both in terms of their development e.g. where offspring were prone to birth defects and had abnormal skeletal formation, and in terms of their surviving at all. Moreover, what was most surprising, was that these effects could still be seen 2 generations later. Epigenetic inheritance of aberrant development can be initiated by histone demethylase activity in developing sperm, without changes to DNA methylation at CpG-rich regions.
Kimmins added, “These findings are remarkable because they indicate that information other than DNA is involved in heritability. The study highlights the critical role that fathers play in the health of their children and even grand-children. Since chemical modifications on histones are susceptible to environmental exposures, the work opens new avenues of investigation for the possible prevention and treatment of diseases of various kinds, affecting health across generations.”
http://www.mcgill.ca/newsroom/channels/news/father-effect-255992
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