Epigenetic transmission of piRNAs through the female germline

In Drosophila, small RNAs bound to Piwi proteins are epigenetic factors transmitted from the mother to the progeny germline. This ensures 'immunization' of progeny against transposable elements.     

Epigenetic Programming： The Challenge to Species Hybridization

In many organisms, the genomes of individual species are isolated by a range of reproductive barriers that act before or after fertilization. Successful mating between species results in the presence of different genomes within a cell （hybridization）, which can lead to incompatibility in cellular events due to adverse genetic interactions. In addition to such genetic interactions, recent studies have shown that the epigenetic control of the genome, silencing of transposons, control of non-additive gene expression and genomic imprinting might also contribute to reproductive barriers in plant and animal species. These genetic and epigenetic mechanisms play a significant role in the prevention of gene flow between species. In this review, we focus on aspects of epigenetic control related to hybrid incompatibility during species hybrid- ization, and also consider key mechanism（s） in the interaction between different genomes.     

Accurate Prediction of Transposon-Derived piRNAs by Integrating Various Sequential and Physicochemical Features

BackgroundPiwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules. The transposon-derived piRNA prediction can enrich the research contents of small ncRNAs as well as help to further understand generation mechanism of gamete.MethodsIn this paper, we attempt to differentiate transposon-derived piRNAs from non-piRNAs based on their sequential and physicochemical features by using machine learning methods. We explore six sequence-derived features, i.e. spectrum profile, mismatch profile, subsequence profile, position-specific scoring matrix, pseudo dinucleotide composition and local structure-sequence triplet elements, and systematically evaluate their performances for transposon-derived piRNA prediction. Finally, we consider two approaches: direct combination and ensemble learning to integrate useful features and achieve high-accuracy prediction models.ResultsWe construct three datasets, covering three species: Human, Mouse and Drosophila, and evaluate the performances of prediction models by 10-fold cross validation. In the computational experiments, direct combination models achieve AUC of 0.917, 0.922 and 0.992 on Human, Mouse and Drosophila, respectively; ensemble learning models achieve AUC of 0.922, 0.926 and 0.994 on the three datasets.ConclusionsCompared with other state-of-the-art methods, our methods can lead to better performances. In conclusion, the proposed methods are promising for the transposon-derived piRNA prediction. The source codes and datasets are available in S1 File.     

Accumulation of piRNAs in the chromatoid bodies purified by a novel isolation protocol

Haploid male germ cells are featured by an intriguing cytoplasmic cloud-like structure that has been named as chromatoid body (CB) on the basis of its staining properties and appearance under a microscope. Notwithstanding its early discovery in the late 19th century, the function of the CB is still largely obscure. Emerging evidence suggests a role for the CB and other similar RNA-containing granules, such as germ plasm in lower organism and processing bodies in somatic cells, in the control and organization of RNA processing and/or storage. Despite the increasing scientific demand, the lack of CB purification protocols has still been the main obstacle in the functional characterization of this structure. We have successfully isolated CBs from mouse testis by a novel immunoaffinity purification procedure and validated by several different methods that pure CB fractions are obtained. Analysis of the CB RNA content reveals enrichment of PIWI-interacting RNAs (piRNAs), further emphasizing the role of CB as the RNA processing body.     

Epigenetic specification of centromeres by CENP-A

Centromeres are the chromosomal loci that direct the formation of the kinetochores. These macromolecular assemblies mediate the interaction between chromosomes and spindle microtubules and thereby power chromosome movement during cell division. They are also the sites of extensive regulation of the chromosome segregation process. Except in the case of budding yeast, centromere identity does not rely on DNA sequence but on the presence of a special nucleosome that contains a histone H3 variant known as CenH3 or CENP-A (Centromere Protein A). It has been therefore proposed that CENP-A is the epigenetic mark of the centromere. Upon DNA replication the mark is diluted two-fold and must be replenished to maintain centromere identity. What distinguishes CENP-A nucleosomes from those containing histone H3, how CENP-A nucleosomes are incorporated specifically into centromeric chromatin, and how this incorporation is coordinated with other cell cycle events are key issues that have been the focus of intensive research over the last decade. Here we review some of the highlights of this research.     

Epigenetic gene regulation by noncoding RNAs

Functional noncoding RNAs have distinct roles in epigenetic gene regulation. Large RNAs have been shown to control gene expression from a single locus (Tsix RNA), from chromosomal regions (Air RNA), and from entire chromosomes (roX and Xist RNAs). These RNAs regulate genes in cis; although the Drosophila roX RNAs can also function in trans. The chromatin modifications mediated by these RNAs can increase or decrease gene expression. These results suggest that the primary role of RNA molecules in epigenetic gene regulation is to restrict chromatin modifications to particular regions of the genome. However, given that RNA has been shown to be at the catalytic core of other ribonucleoprotein complexes, it is also possible that RNA also plays a role in modulating changes in chromatin structure.     

Genetic Variation Stimulated by Epigenetic Modification

Homologous recombination is essential for maintaining genomic integrity. A common repair mechanism, it uses a homologous or homeologous donor as a template for repair of a damaged target gene. Such repair must be regulated, both to identify appropriate donors for repair, and to avoid excess or inappropriate recombination. We show that modifications of donor chromatin structure can promote homology-directed repair. These experiments demonstrate that either the activator VP16 or the histone chaperone, HIRA, accelerated gene conversion approximately 10-fold when tethered within the donor array for Ig gene conversion in the chicken B cell line DT40. VP16 greatly increased levels of acetylated histones H3 and H4, while tethered HIRA did not affect histone acetylation, but caused an increase in local nucleosome density and levels of histone H3.3. Thus, epigenetic modification can stimulate genetic variation. The evidence that distinct activating modifications can promote similar functional outcomes suggests that a variety of chromatin changes may regulate homologous recombination, and that disregulation of epigenetic marks may have deleterious genetic consequences.