Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions

Abstract

BackgroundEnvironmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes, suggesting a general alteration in genome activity.ResultsInvestigation of different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had transgenerational transcriptomes. The microarrays from 11 different tissues were compared with a gene bionetwork analysis. Although each tissue transgenerational transcriptome was unique, common cellular pathways and processes were identified between the tissues. A cluster analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue-specific gene expression and function. A large number of statistically significant over-represented clusters of genes were identified in the genome for both males and females. These gene clusters ranged from 2-5 megabases in size, and a number of them corresponded to the epimutations previously identified in sperm that transmit the epigenetic transgenerational inheritance of disease phenotypes.ConclusionsCombined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome may coordinately regulate these tissue-specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes.

Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm

“…Epigenetic polymorphism has attracted enormous interest in recent years. Several recent studies investigating the connection between genetic variation and epigenetic variation revealed that epigenetic polymorphisms are likely the result of a complex interplay between genetic and environmental factors (Anway et al 2005;Li et al 2011;Crews et al 2012;Skinner et al 2012). Our finding provides additional support for the potential functional impact of epigenetic polymorphisms.…”

“…Unlike genetic polymorphisms such as SNPs and copy number variation, epigenetic polymorphisms can be influenced by both genetic and environmental determinants (Anway et al 2005;Li et al 2011;Crews et al 2012;Skinner et al 2012). In our study, we obtained biological replicates from two individuals for the breast, fetal brain, and blood data sets.…”

Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for prospermatogonial development in mice

“…These RNA samples were then subjected to labeling, hybridization, washing, data acquisition and analyses as described previously. 57 Bioinformatic analysis. For piRNA-mRNA mapping, coding sequences (CDS), 3 0 UTRs, and 5 0 UTRs for all up or downregulated mRNAs with Po0.05 and fold change 41.2 (a total of 2161 genes) and 3290 randomly chosen mRNAs determined to be unregulated by MIWI2 in our microarray analyses were collected from ENSEMBL database (release 71).…”

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

“…The inherited changes were monitored in the third generation after treatment (13–15). Effects on DNA methylation reprogramming were suggested as a major mechanism for transgenerational inheritance of chromatin modifications.…”