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Apomixis is a form of asexual reproduction through seeds in angiosperms. Apomictic plants bypass meiosis and fertilization, developing offspring that are genetically identical to their mother. In a genetic screen for maize (Zea mays) mutants mimicking aspects of apomixis, we identified a dominant mutation resulting in the formation of functional unreduced gametes. The mutant shows defects in chromatin condensation during meiosis and subsequent failure to segregate chromosomes. The mutated locus codes for AGO104, a member of the ARGONAUTE family of proteins. AGO104 accumulates specifically in somatic cells surrounding the female meiocyte, suggesting a mobile signal rather than cellautonomous control. AGO104 is necessary for non-CG methylation of centromeric and knob-repeat DNA. Digital gene expression tag profiling experiments using high-throughput sequencing show that AGO104 influences the transcription of many targets in the ovaries, with a strong effect on centromeric repeats. AGO104 is related to Arabidopsis thaliana AGO9, but while AGO9 acts to repress germ cell fate in somatic tissues, AGO104 acts to repress somatic fate in germ cells. Our findings show that female germ cell development in maize is dependent upon conserved small RNA pathways acting noncell-autonomously in the ovule. Interfering with this repression leads to apomixis-like phenotypes in maize.

BackgroundMalnutrition is a major factor affecting animal health, resistance to disease and survival. In honey bees (Apis mellifera), pollen, which is the main dietary source of proteins, amino acids and lipids, is essential to adult bee physiological development while reducing their susceptibility to parasites and pathogens. However, the molecular mechanisms underlying pollen's nutritive impact on honey bee health remained to be determined. For that purpose, we investigated the influence of pollen nutrients on the transcriptome of worker bees parasitized by the mite Varroa destructor, known for suppressing immunity and decreasing lifespan. The 4 experimental groups (control bees without a pollen diet, control bees fed with pollen, varroa-parasitized bees without a pollen diet and varroa-parasitized bees fed with pollen) were analyzed by performing a digital gene expression (DGE) analysis on bee abdomens.ResultsAround 36, 000 unique tags were generated per DGE-tag library, which matched about 8, 000 genes (60% of the genes in the honey bee genome). Comparing the transcriptome of bees fed with pollen and sugar and bees restricted to a sugar diet, we found that pollen activates nutrient-sensing and metabolic pathways. In addition, those nutrients had a positive influence on genes affecting longevity and the production of some antimicrobial peptides. However, varroa parasitism caused the development of viral populations and a decrease in metabolism, specifically by inhibiting protein metabolism essential to bee health. This harmful effect was not reversed by pollen intake.ConclusionsThe DGE-tag profiling methods used in this study proved to be a powerful means for analyzing transcriptome variation related to nutrient intake in honey bees. Ultimately, with such an approach, applying genomics tools to nutrition research, nutrigenomics promises to offer a better understanding of how nutrition influences body homeostasis and may help reduce the susceptibility of bees to (less virulent) pathogens.

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B lymphocytes from patients with systemic lupus erythematosus (SLE) are characterized by reduced expression levels of membrane CD5. Recent studies from our laboratory have revealed that the level of membrane CD5 is determined by the relative level of two alternative CD5 isoforms; CD5-E1A, which is expressed on the membrane, and CD5-E1B, which is retained in the cytoplasm. Using bisulfite sequencing and methylation-sensitive endonuclease assays we show that the promoter for the alternative CD5-E1B isoform is demethylated in B cells from patients with SLE but not in healthy controls. We go on to show that differential methylation is more pronounced following BCR engagement. As a result of this demethylation, CD5-E1B mRNA is transcribed at the expense of CD5-E1A mRNA transcription. We provide further evidence that production of high IL-6 levels by SLE B cells abrogates the ability of SLE B cells to induce DNA methyl transferase (DNMT1) and then to methylate DNA, an effect that is reversed in the presence of a blocking Ab to the IL-6 receptor. S ystemic lupus erythematosus (SLE)4 is associated with diverse clinical manifestations (1). The main features of autoimmunity in SLE are B cell hyperactivity, spontaneous lymphocyte proliferation, and the production of pathogenic Abs to self-Ags. B cell abnormalities in SLE also include excess cytokine production, autoantigen presentation to T cells and modulation of the function of other immune cells (2). Thus, SLE is generally considered a B cell disease, a theme strengthened by the efficacy of therapies targeting B cells. For example, therapeutic approaches using depleting anti-CD20 has proved to be highly beneficial in treatment of SLE (3). Further, neutralization of cytokines that promote B cell responses such as IL-6, or interruption of cognate T cell and B cell interactions has been successful in early clinical trials (4,5). All this provides the rationale for further investigation of mechanisms of B cell involvement in driving autoimmunity and to develop more selective therapeutic targets.The central role played by B cells in immunity necessitates that its responses are tightly regulated. B cell responses are initiated by signaling through the BCR. Signaling initiated following BCR engagement is regulated by coreceptors and by a network of protein tyrosine kinases and phosphatases. Recent findings suggest that defects in BCR-mediated signaling can result in lupus autoimmunity. For example, there is an association between SLE autoimmunity and mutations in a number of genes that encode B cellspecific signaling molecules including protein tyrosine kinases, non-receptor phosphatase type 22, B cell scaffold protein with ankyrin repeats 1 and the inhibitory IgG Fc␥RIIb (6). In addition to direct evidence for the effect of mutations in signaling molecules on BCR-mediated signaling, the contribution of epigenetic factors has also been proposed (7). The most commonly observed epigenetic abnormality implicated in SLE pathology is altered DNA methylation at the 5-carbon positio...

Genomic imprinting is an epigenetic mechanism that restrains the expression of~100 eutherian genes in a parent-of-originspecific manner. The reason for this selective targeting of genes with seemingly disparate molecular functions is unclear. In the present work, we show that imprinted genes are coexpressed in a network that is regulated at the transition from proliferation to quiescence and differentiation during fibroblast cell cycle withdrawal, adipogenesis in vitro, and muscle regeneration in vivo. Imprinted gene regulation is not linked to alteration of DNA methylation or to perturbation of monoallelic, parent-oforigin-dependent expression. Overexpression and knockdown of imprinted gene expression alters the sensitivity of preadipocytes to contact inhibition and adipogenic differentiation. In silico and in cellulo experiments showed that the imprinted gene network includes biallelically expressed, nonimprinted genes. These control the extracellular matrix composition, cell adhesion, cell junction, and extracellular matrix-activated and growth factor-activated signaling. These observations show that imprinted genes share a common biological process that may account for their seemingly diverse roles in embryonic development, obesity, diabetes, muscle physiology, and neoplasm.

ANISEED (www.aniseed.cnrs.fr) is the main model organism database for tunicates, the sister-group of vertebrates. This release gives access to annotated genomes, gene expression patterns, and anatomical descriptions for nine ascidian species. It provides increased integration with external molecular and taxonomy databases, better support for epigenomics datasets, in particular RNA-seq, ChIP-seq and SELEX-seq, and features novel interactive interfaces for existing and novel datatypes. In particular, the cross-species navigation and comparison is enhanced through a novel taxonomy section describing each represented species and through the implementation of interactive phylogenetic gene trees for 60% of tunicate genes. The gene expression section displays the results of RNA-seq experiments for the three major model species of solitary ascidians. Gene expression is controlled by the binding of transcription factors to cis-regulatory sequences. A high-resolution description of the DNA-binding specificity for 131 Ciona robusta (formerly C. intestinalis type A) transcription factors by SELEX-seq is provided and used to map candidate binding sites across the Ciona robusta and Phallusia mammillata genomes. Finally, use of a WashU Epigenome browser enhances genome navigation, while a Genomicus server was set up to explore microsynteny relationships within tunicates and with vertebrates, Amphioxus, echinoderms and hemichordates.

Asexual propagation and whole body regeneration are forms of nonembryonic development (NED) widespread across animal phyla and central in life history and evolutionary diversification of metazoans. Whereas it is challenging to reconstruct the gains or losses of NED at large phylogenetic scale, comparative studies could benefit from being conducted at more restricted taxonomic scale, in groups for which phylogenetic relationships are well established. The ascidian family of Styelidae encompasses strictly sexually reproducing solitary forms as well as colonial species that combine sexual reproduction with different forms of NED. To date, the phylogenetic relationships between colonial and solitary styelids remain controversial and so is the pattern of NED evolution. In this study, we built an original pipeline to combine eight genomes with 18 de novo assembled transcriptomes and constructed data sets of unambiguously orthologous genes. Using a phylogenomic super-matrix of 4,908 genes from these 26 tunicates we provided a robust phylogeny of this family of chordates, which supports two convergent acquisitions of NED. This result prompted us to further describe the budding process in the species Polyandrocarpa zorritensis, leading to the discovery of a novel mechanism of asexual development. Whereas the pipeline and the data sets produced can be used for further phylogenetic reconstructions in tunicates, the phylogeny provided here sets an evolutionary framework for future experimental studies on the emergence and disappearance of complex characters such as asexual propagation and whole body regeneration.