The Polycomb Group Protein EED Is Dispensable for the Initiation of Random X-Chromosome Inactivation

The Polycomb group (PcG) proteins are thought to silence gene expression by modifying chromatin. The Polycomb repressive complex 2 (PRC2) plays an essential role in mammalian X-chromosome inactivation (XCI), a model system to investigate heritable gene silencing. In the mouse, two different forms of XCI occur. In the preimplantation embryo, all cells undergo imprinted inactivation of the paternal X-chromosome (Xp). During the peri-implantation period, cells destined to give rise to the embryo proper erase the imprint and randomly inactivate either the maternal X-chromosome or the Xp; extraembryonic cells, on the other hand, maintain imprinted XCI of the Xp. PRC2 proteins are enriched on the inactive-X during early stages of both imprinted and random XCI. It is therefore thought that PRC2 contributes to the initiation of XCI. Mouse embryos lacking the essential PRC2 component EED harbor defects in the maintenance of imprinted XCI in differentiating trophoblast cells. Assessment of PRC2 requirement in the initiation of XCI, however, has been hindered by the presence of maternally derived proteins in the early embryo. Here we show that Eed (−/−) embryos initiate and maintain random XCI despite lacking any functional EED protein prior to the initiation of random XCI. Thus, despite being enriched on the inactive X-chromosome, PcGs appear to be dispensable for the initiation and maintenance of random XCI. These results highlight the lineage- and differentiation state–specific requirements for PcGs in XCI and argue against PcG function in the formation of the facultative heterochromatin of the inactive X-chromosome

X Chromosome Reactivation Initiates in Nascent Primordial Germ Cells in Mice

During primordial germ cell (PGC) development, epigenetic reprogramming events represented by X chromosome reactivation and erasure of genomic imprinting are known to occur. Although precise timing is not given, X reactivation is thought to take place over a short period of time just before initiation of meiosis. Here, we show that the cessation of Xist expression commences in nascent PGCs, and re-expression of some X-linked genes begins in newly formed PGCs. The X reactivation process was not complete in E14.5 PGCs, indicating that X reactivation in developing PGCs occurs over a prolonged period. These results set the reactivation timing much earlier than previously thought and suggest that X reactivation may involve slow passive steps

Retrotransposons and germ cells: reproduction, death, and diversity

The evolutionary success of retrotransposable elements is reflected by their abundance in mammalian genomes. To restrict their further advance, a number of defence mechanisms have been put in place by the host. These seem to be particularly effective in the germ line while somatic lineages might be more permissive to new insertions, as recent work by Kano and colleagues suggests

A climate network perspective on the intertropical convergence zone

The intertropical convergence zone (ITCZ) is an important component of the tropical rain belt. Climate models continue to struggle to adequately represent the ITCZ and differ substantially in its simulated response to climate change. Here we employ complex network approaches, which extract spatiotemporal variability patterns from climate data, to better understand differences in the dynamics of the ITCZ in state-of-the-art global circulation models (GCMs). For this purpose, we study simulations with 14 GCMs in an idealized slab-ocean aquaplanet setup from TRACMIP – the Tropical Rain belts with an Annual cycle and a Continent Model Intercomparison Project. We construct network representations based on the spatial correlation patterns of monthly surface temperature anomalies and study the zonal-mean patterns of different topological and spatial network characteristics. Specifically, we cluster the GCMs by means of the distributions of their zonal network measures utilizing hierarchical clustering. We find that in the control simulation, the distributions of the zonal network measures are able to pick up model differences in the tropical sea surface temperature (SST) contrast, the ITCZ position, and the strength of the Southern Hemisphere Hadley cell. Although we do not find evidence for consistent modifications in the network structure tracing the response of the ITCZ to global warming in the considered model ensemble, our analysis demonstrates that coherent variations of the global SST field are linked to ITCZ dynamics. This suggests that climate networks can provide a new perspective on ITCZ dynamics and model differences therein

A climate network perspective on the intertropical convergence zone

The intertropical convergence zone (ITCZ) is an important component of the tropical rain belt. Climate models continue to struggle to adequately represent the ITCZ and differ substantially in its simulated response to climate change. Here we employ complex network approaches, which extract spatiotemporal variability patterns from climate data, to better understand differences in the dynamics of the ITCZ in state-of-the-art global circulation models (GCMs). For this purpose, we study simulations with 14 GCMs in an idealized slab-ocean aquaplanet setup from TRACMIP – the Tropical Rain belts with an Annual cycle and a Continent Model Intercomparison Project. We construct network representations based on the spatial correlation patterns of monthly surface temperature anomalies and study the zonal-mean patterns of different topological and spatial network characteristics. Specifically, we cluster the GCMs by means of the distributions of their zonal network measures utilizing hierarchical clustering. We find that in the control simulation, the distributions of the zonal network measures are able to pick up model differences in the tropical sea surface temperature (SST) contrast, the ITCZ position, and the strength of the Southern Hemisphere Hadley cell. Although we do not find evidence for consistent modifications in the network structure tracing the response of the ITCZ to global warming in the considered model ensemble, our analysis demonstrates that coherent variations of the global SST field are linked to ITCZ dynamics. This suggests that climate networks can provide a new perspective on ITCZ dynamics and model differences therein

Self-organisation of plasticity and specialisation in a primitively social insect

Biological systems have the capacity to not only build and robustly maintain complex structures but also to rapidly break up and rebuild such structures. Here, using primitive societies of Polistes wasps, we show that both robust specialization and rapid plasticity are emergent properties of multi-scale dynamics. We combine theory with experiments that, after perturbing the social structure by removing the queen, correlate time-resolved multi-omics with video recordings. We show that the queen-worker dimorphism relies on the balance between the development of a molecular queen phenotype in all insects and colony-scale inhibition of this phenotype via asymmetric interactions. This allows Polistes to be stable against intrinsic perturbations of molecular states while reacting plastically to extrinsic cues affecting the whole society. Long-term stability of the social structure is reinforced by dynamic DNA methylation. Our study provides a general principle of how both specialization and plasticity can be achieved in biological systems. A record of this paper’s transparent peer review process is included in the supplemental information

Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo

DNA methylomes are extensively reprogrammed during mouse pre-implantation and early germ cell development. The main feature of this reprogramming is a genome-wide decrease in 5-methylcytosine (5mC). Standard high-resolution single-stranded bisulfite sequencing techniques do not allow discrimination of the underlying passive (replication-dependent) or active enzymatic mechanisms of 5mC loss. We approached this problem by generating high-resolution deep hairpin bisulfite sequencing (DHBS) maps, allowing us to follow the patterns of symmetric DNA methylation at CpGs dyads on both DNA strands over single replications.We compared DHBS maps of repetitive elements in the developing zygote, the early embryo, and primordial germ cells (PGCs) at defined stages of development. In the zygote, we observed distinct effects in paternal and maternal chromosomes. A significant loss of paternal DNA methylation was linked to replication and to an increase in continuous and dispersed hemimethylated CpG dyad patterns. Overall methylation levels at maternal copies remained largely unchanged, but showed an increased level of dispersed hemi-methylated CpG dyads. After the first cell cycle, the combined DHBS patterns of paternal and maternal chromosomes remained unchanged over the next three cell divisions. By contrast, in PGCs the DNA demethylation process was continuous, as seen by a consistent decrease in fully methylated CpG dyads over consecutive cell divisions.The main driver of DNA demethylation in germ cells and in the zygote is partial impairment of maintenance of symmetric DNA methylation at CpG dyads. In the embryo, this passive demethylation is restricted to the first cell division, whereas it continues over several cell divisions in germ cells. The dispersed patterns of CpG dyads in the early-cleavage embryo suggest a continuous partial (and to a low extent active) loss of methylation apparently compensated for by selective de novo methylation. We conclude that a combination of passive and active demethylation events counteracted by de novo methylation are involved in the distinct reprogramming dynamics of DNA methylomes in the zygote, the early embryo, and PGCs

Increased placental glucose transport rates in pregnant mice carrying fetuses with targeted disruption of their placental-specific Igf2 transcripts are not associated with raised circulating glucose concentrations.

At the beginning of the third week of pregnancy, mouse fetuses with targeted disruption of their paternally-transmitted insulin-like growth factor 2 gene placental-specific transcripts have growth-restricted placentas but normal body weights due to upregulated placental nutrient transport. We assessed whether increased placental glucose transport rates were associated with raised maternal glucose concentrations by performing intraperitoneal glucose tolerance tests (ipGTT) in pregnant mice carrying knockout pups and comparing them with mice carrying genotype-matched phenotypically wild type pups. Mean ± SD body weights of affected pups were 95 ± 8% of control values at e16 and 73 ± 7% at e18. There were no differences in areas under the maternal ipGTT curves at either e16 (mean ± SD being 99.0 ± 9.1% of control values; P = .9) or e18 (91.4 ± 13.4%; P = .3), suggesting that effects on transplacental glucose transport in these mice are not mediated through changes in maternal glucose concentrations

Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass.

Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.This work was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation (SNF)/Novartis SNF (F.v.M.) and core funding to the Cambridge Stem Cell Institute from the Wellcome Trust and Medical Research Council. AS is a Medical Research Council Professor.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.stemcr.2016.02.00