Spaceflight-Induced Gene Expression Profiles in the Mouse Brain Are Attenuated by Treatment with the Antioxidant BuOE.

The demands of deep space pose a health risk to the central nervous system that has long been a concern when sending humans to space. While little is known about how spaceflight affects transcription spatially in the brain, a greater understanding of this process has the potential to aid strategies that mitigate the effects of spaceflight on the brain. Therefore, we performed GeoMx Digital Spatial Profiling of mouse brains subjected to either spaceflight or grounded controls.

Characterization of a strain-specific CD-1 reference genome reveals potential inter- and intra-strain functional variability.

Background: CD-1 is an outbred mouse stock that is frequently used in toxicology, pharmacology, and fundamental biomedical research. Although inbred strains are typically better suited for such studies due to minimal genetic variability, outbred stocks confer practical advantages over inbred strains, such as improved breeding performance and low cost. Knowledge of the full genetic variability of CD-1 would make it more useful in toxicology, pharmacology, and fundamental biomedical research.

The Nab2 RNA binding protein inhibits mA methylation and male-specific splicing of transcript in female neuronal tissue.

The polyadenosine RNA binding protein Nab2, which is orthologous to a human protein lost in a form of inherited intellectual disability, controls adult locomotion, axon projection, dendritic arborization, and memory through a largely undefined set of target RNAs. Here, we show a specific role for Nab2 in regulating splicing of ~150 exons/introns in the head transcriptome and focus on retention of a male-specific exon in the sex determination factor () that is enriched in female neurons. Previous studies have revealed that this splicing event is regulated in females by N6-methyladenosine (mA) modification by the Mettl3 complex.

Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes.

Background: Fetal hypoxia causes vital, systemic, developmental malformations in the fetus, particularly in the brain, and increases the risk of diseases in later life. We previously demonstrated that fetal hypoxia exposure increases the susceptibility of the neonatal brain to hypoxic-ischemic insult. Herein, we investigate the effect of fetal hypoxia on programming of cell-specific transcriptomes in the brain of neonatal rats.

A budding yeast model for human disease mutations in the cap subunit of the RNA exosome complex.

RNA exosomopathies, a growing family of diseases, are linked to missense mutations in genes encoding structural subunits of the evolutionarily conserved, 10-subunit exoribonuclease complex, the RNA exosome. This complex consists of a three-subunit cap, a six-subunit, barrel-shaped core, and a catalytic base subunit. While a number of mutations in RNA exosome genes cause pontocerebellar hypoplasia, mutations in the cap subunit gene cause an apparently distinct clinical presentation that has been defined as a novel syndrome SHRF (hort stature, earing loss, etinitis pigmentosa, and distinctive acies).

A Drosophila model of Pontocerebellar Hypoplasia reveals a critical role for the RNA exosome in neurons.

The RNA exosome is an evolutionarily-conserved ribonuclease complex critically important for precise processing and/or complete degradation of a variety of cellular RNAs. The recent discovery that mutations in genes encoding structural RNA exosome subunits cause tissue-specific diseases makes defining the role of this complex within specific tissues critically important. Mutations in the RNA exosome component 3 (EXOSC3) gene cause Pontocerebellar Hypoplasia Type 1b (PCH1b), an autosomal recessive neurologic disorder.

Protection from DNA re-methylation by transcription factors in primordial germ cells and pre-implantation embryos can explain trans-generational epigenetic inheritance.

Background: A growing body of evidence suggests that certain epiphenotypes can be passed across generations via both the male and female germlines of mammals. These observations have been difficult to explain owing to a global loss of the majority of known epigenetic marks present in parental chromosomes during primordial germ cell development and after fertilization.

Results: By integrating previously published BS-seq, DNase-seq, ATAC-seq, and RNA-seq data collected during multiple stages of primordial germ cell and pre-implantation development, we find that the methylation status of the majority of CpGs genome-wide is restored after global de-methylation, despite the fact that global CpG methylation drops to 10% in primordial germ cells and 20% in the inner cell mass of the blastocyst.

Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington's Disease Monkey pluripotent stem cells.

Background: Huntington's Disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion, resulting in a mutant huntingtin protein. While it is now clear that astrocytes are affected by HD and significantly contribute to neuronal dysfunction and pathogenesis, the alterations in the transcriptional and epigenetic profiles in HD astrocytes have yet to be characterized. Here, we examine global transcription and chromatin accessibility dynamics during in vitro astrocyte differentiation in a transgenic non-human primate model of HD.

Ecdysone-Induced 3D Chromatin Reorganization Involves Active Enhancers Bound by Pipsqueak and Polycomb.

Evidence suggests that Polycomb (Pc) is present at chromatin loop anchors in Drosophila. Pc is recruited to DNA through interactions with the GAGA binding factors GAF and Pipsqueak (Psq). Using HiChIP in Drosophila cells, we find that the psq gene, which has diverse roles in development and tumorigenesis, encodes distinct isoforms with unanticipated roles in genome 3D architecture.

Maintenance of CTCF- and Transcription Factor-Mediated Interactions from the Gametes to the Early Mouse Embryo.

The epigenetic information present in mammalian gametes and whether it is transmitted to the progeny are relatively unknown. We find that many promoters in mouse sperm are occupied by RNA polymerase II (Pol II) and Mediator. The same promoters are accessible in GV and MII oocytes and preimplantation embryos.

A Quantitative Profiling Tool for Diverse Genomic Data Types Reveals Potential Associations between Chromatin and Pre-mRNA Processing.

High-throughput sequencing, and genome-based datasets in general, are often represented as profiles centered at reference points to study the association of protein binding and other signals to particular regulatory mechanisms. Although these profiles often provide compelling evidence of these associations, they do not provide a quantitative assessment of the enrichment, which makes the comparison between signals and conditions difficult. In addition, a number of biases can confound profiles, but are rarely accounted for in the tools currently available.

Age-changes in gene expression in primary mixed glia cultures from young vs. old rat cerebral cortex are modified by interactions with neurons.

Astrocytic GFAP expression increases during normal aging in many brain regions and in primary astrocyte cultures derived from aging rodent brains. As shown below, we unexpectedly found that the age-related increase of GFAP expression was suppressed in mixed glia (astrocytes+microglia). However, the age-related increase of GFAP was observed when E18 neurons were co-cultured with mixed glia.

Observation of the radiative decay mode of the free neutron.

The theory of quantum electrodynamics (QED) predicts that beta decay of the neutron into a proton, electron and antineutrino should be accompanied by a continuous spectrum of soft photons. While this inner bremsstrahlung branch has been previously measured in nuclear beta and electron capture decay, it has never been observed in free neutron decay. Recently, the photon energy spectrum and branching ratio for neutron radiative decay have been calculated using two approaches: a standard QED framework and heavy baryon chiral perturbation theory (an effective theory of hadrons based on the symmetries of quantum chromodynamics).