Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency

Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation

Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naïve pluripotency

Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation

BPA disrupts meiosis I in oogonia by acting on pathways including cell cycle regulation, meiosis initiation and spindle assembly

This work was supported by funding to PAF and CC from the Wellcome Trust (080388) and the European Community's Seventh Framework Programme under grant agreement no. 212885. (http://www.abdn.ac.uk/reef/). The authors would like to thank INRAE, SAAJ, experimental animal facility (Sciences de l'Animal et de l'Aliment de Jouy), especially Jean-Pierre Albert, Didier Mauchand, and Jean-François Alkombre.Peer reviewedPublisher PD

Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency.

Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation

Efficient eco-friendly inverted quantum dot sensitized solar cells

Recent progress in quantum dot (QD) sensitized solar cells has demonstrated the possibility of low-cost and efficient photovoltaics. However, the standard device structure based on n-type materials often suffers from slow hole injection rate, which may lead to unbalanced charge transport. We have fabricated efficient p-type (inverted) QD sensitized cells, which combine the advantages of conventional QD cells with p-type dye sensitized configurations. Moreover, p-type QD sensitized cells can be used in highly promising tandem configurations with n-type ones. QDs without toxic Cd and Pb elements and with improved absorption and stability were successfully deposited onto mesoporous NiO electrode showing good coverage and penetration according to morphological analysis. Detailed photophysical charge transfer studies showed that high hole injection rates (108 s−1) observed in such systems are comparable with electron injection in conventional n-type QD assemblies. Inverted solar cells fabricated with various QDs demonstrate excellent power conversion efficiencies of up to 1.25%, which is 4 times higher than the best values for previous inverted QD sensitized cells. Attempts to passivate the surface of the QDs show that traditional methods of reduction of recombination in the QD sensitized cells are not applicable to the inverted architectures

Skin manifestations among GATA2-deficient patients

International audienceGATA2 mutations have been identified in various diseases, such as MonoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukaemia and dendritic cell, monocyte, B-cell and natural killer-cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of patients with GATA2 mutations have dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. We report three patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described gingival hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial lesions. Dermatologists can encounter patients with GATA2 mutations and should recognize this disorder

Effect of maternal obesity and preconceptional weight loss on male and female offspring metabolism and olfactory performance in mice

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours

AKT activity orchestrates marginal zone B cell development in mice and humans.

The signals controlling marginal zone (MZ) and follicular (FO) B cell development remain incompletely understood. Here, we show that AKT orchestrates MZ B cell formation in mice and humans. Genetic models that increase AKT signaling in B cells or abolish its impact on FoxO transcription factors highlight the AKT-FoxO axis as an on-off switch for MZ B cell formation in mice. In humans, splenic immunoglobulin (Ig) D <sup>+</sup> CD27 <sup>+</sup> B cells, proposed as an MZ B cell equivalent, display higher AKT signaling than naive IgD <sup>+</sup> CD27 <sup>-</sup> and memory IgD <sup>-</sup> CD27 <sup>+</sup> B cells and develop in an AKT-dependent manner from their precursors in vitro, underlining the conservation of this developmental pathway. Consistently, CD148 is identified as a receptor indicative of the level of AKT signaling in B cells, expressed at a higher level in MZ B cells than FO B cells in mice as well as humans

Ultrastructure of macromolecular assemblies contributing to bacterial spore resistance revealed by in situ cryo-electron tomography

Bacterial spores owe their incredible resistance capacities to molecular structures that protect the cell content from external aggressions. Among the determinants of resistance are the quaternary structure of the chromosome and an extracellular shell made of proteinaceous layers (the coat), the assembly of which remains poorly understood. Here, in situ cryo-electron tomography on lamellae generated by cryo-focused ion beam micromachining provides insights into the ultrastructural organization of Bacillus subtilis sporangia. The reconstructed tomograms reveal that early during sporulation, the chromosome in the forespore adopts a toroidal structure harboring 5.5-nm thick fibers. At the same stage, coat proteins at the surface of the forespore form a stack of amorphous or structured layers with distinct electron density, dimensions and organization. By analyzing mutant strains using cryo-electron tomography and transmission electron microscopy on resin sections, we distinguish seven nascent coat regions with different molecular properties, and propose a model for the contribution of coat morphogenetic proteins