Partial inactivation of PLK-1 in the embryo leads to the formation of two nuclei containing either maternal or paternal chromosomes. This is due to a defect in forming a nuclear envelope gap at the interface of the maternal and paternal pronuclei. Moreover, this gap formation is linked to proper chromosome alignment during the first mitosis.

Paternal epigenetic inheritance is gaining attention for its growing medical relevance. However, the form in which paternal epigenetic information is transmitted to offspring and how it influences offspring development remain poorly understood. Here we show that in C. elegans, sperm-inherited chromatin states transmitted to the primordial germ cells in offspring influence germline transcription and development. We show that sperm chromosomes inherited lacking the repressive histone modification H3K27me3 are maintained in that state by H3K36me3 antagonism. Inheritance of H3K27me3-lacking sperm chromosomes results in derepression in the germline of somatic genes, especially neuronal genes, predominantly from sperm-inherited alleles. This results in germ cells primed for losing their germ cell identity and adopting a neuronal fate. These data demonstrate that histone modifications are one mechanism through which epigenetic information from a father can shape offspring gene expression and development.

The transmission of chromatin states from parent cells to daughter cells preserves cell-specific transcriptional states and thus cell identity through cell division. The mechanism that underpins this process is not fully understood. The role that chromatin states serve in transmitting gene expression information across generations via sperm and oocytes is even less understood. Here, we utilized a model in which Caenorhabditis elegans sperm and oocyte alleles were inherited in different states of the repressive mark H3K27me3. This resulted in the alleles achieving different transcriptional states within the nuclei of offspring. Using this model, we showed that sperm alleles inherited without H3K27me3 were sensitive to up-regulation in offspring somatic and germline tissues, and tissue context determined which genes were up-regulated. We found that the subset of sperm alleles that were up-regulated in offspring germlines retained the H3K27me3(−) state and were transmitted to grandoffspring as H3K27me3(−) and up-regulated epialleles, demonstrating that H3K27me3 can serve as a transgenerational epigenetic carrier in C. elegans .

Transcriptomic approaches have provided a growing set of powerful tools with which to study genome-wide patterns of gene expression. Rapidly evolving technologies enable analysis of transcript abundance data from particular tissues and even single cells. This Primer discusses methods that can be used to collect and profile RNAs from specific tissues or cells, process and analyze high-throughput RNA-sequencing data, and define sets of genes that accurately represent a category, such as tissue-enriched or tissue-specific gene expression.

Non-enzymatic reactions in glycolysis lead to the accumulation of methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been suggested to drive obesity- and aging-associated pathologies. We observe that a combination of nicotinamide, lipoic acid, thiamine, pyridoxamine and piperine, which were selected to lower glycation (Gly-Low), reduce toxic glycolytic byproducts, MGO and MGO-derived AGE, MG-H1. Administration of Gly-Low reduced food consumption and body weight, improving insulin sensitivity and survival in both leptin receptor deficient (Lepr db) and wildtype C57 control mouse models. Unlike calorie restriction, Gly-Low inhibited ghrelin-mediated hunger responses and upregulated Tor pathway signaling in the hypothalamus. Gly-Low also extended lifespan when administered as a late life intervention, suggesting its potential benefits in ameliorating age-associated decline by inducing voluntary calorie restriction and reducing glycation.