Question

The germline mutation rates tend to increase along with higher H3K9me3 levels (a type of histone). Please support this with specific examples (ie genes that have high germline mutation rates and have high H3K9me3 levels)

Answer 1

Mutation is important in evolutionary processes, that has both beneficial and adverse consequences. Mutation is associated with genes or chromosomes. However, according to some recent studies, it has been evident that several factors determine the rate of mutation rates, like chromatin organization, GC content, CpG methylation, replication timing, transcriptional levels, expression levels. These factors also vary in their effect with respect to somatic and germ cell lines.

Germline mutations are related to heritability, and heritable variation like susceptibility to heritable diseases, tumors or cancers. Thus, characterization of factors affecting germline mutations, is of very important.

For determination of factors affecting germline mutations, H3K9me3 (Trimethyl modification of histone-3 Lysine-9) can be considered as histone mark.

Previously, H3K9me3 is noted to be associated with more than 40% rate variation in somatic mutations of tumors.

Considering the example of De Novo mutations (DNMs) in human germline cells: Tissues from maternal germline-ovary and paternal germline-testis tissues. The histone mark level in ovary and testes germline cells (exomes) were determined. The increased level of mutation was observed with increased histone marl leves, especially in ovary cells. These results may be attributed to transcriptional gene silencing of H3K9me3.