DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions

<p>Abstract</p> <p>Background</p> <p>Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA), and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes) has not been comprehensively analyzed.</p> <p>Results</p> <p>We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs). These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain.</p> <p>Conclusions</p> <p>A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions.</p

Ice sheet history in the southern part of the Soya Coast, East Antarctica revealed by glacial landforms and surface exposure dating

The Tenth Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 4 Dec. / 3F Seminar room, National Institute of Polar Researc

Multiple episodes of ice loss from the Wilkes Subglacial Basin during the Last Interglacial

The Last Interglacial (LIG: 130,000–115,000 years ago) was a period of warmer global mean temperatures and higher and more variable sea levels than the Holocene (11,700–0 years ago). Therefore, a better understanding of Antarctic ice-sheet dynamics during this interval would provide valuable insights for projecting sea-level change in future warming scenarios. Here we present a high-resolution record constraining ice-sheet changes in the Wilkes Subglacial Basin (WSB) of East Antarctica during the LIG, based on analysis of sediment provenance and an ice melt proxy in a marine sediment core retrieved from the Wilkes Land margin. Our sedimentary records, together with existing ice-core records, reveal dynamic fluctuations of the ice sheet in the WSB, with thinning, melting, and potentially retreat leading to ice loss during both early and late stages of the LIG. We suggest that such changes along the East Antarctic Ice Sheet margin may have contributed to fluctuating global sea levels during the LIG

A High-Speed Congenic Strategy Using First-Wave Male Germ Cells

BACKGROUND: In laboratory mice and rats, congenic breeding is essential for analyzing the genes of interest on specific genetic backgrounds and for analyzing quantitative trait loci. However, in theory it takes about 3-4 years to achieve a strain carrying about 99% of the recipient genome at the tenth backcrossing (N10). Even with marker-assisted selection, the so-called 'speed congenic strategy', it takes more than a year at N4 or N5. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new high-speed congenic system using round spermatids retrieved from immature males (22-25 days of age). We applied the technique to three genetically modified strains of mice: transgenic (TG), knockin (KI) and N-ethyl-N-nitrosourea (ENU)-induced mutants. The donor mice had mixed genetic backgrounds of C57BL/6 (B6):DBA/2 or B6:129 strains. At each generation, males used for backcrossing were selected based on polymorphic marker analysis and their round spermatids were injected into B6 strain oocytes. Backcrossing was repeated until N4 or N5. For the TG and ENU-mutant strains, the N5 generation was achieved on days 188 and 190 and the proportion of B6-homozygous loci was 100% (74 markers) and 97.7% (172/176 markers), respectively. For the KI strain, N4 was achieved on day 151, all the 86 markers being B6-homozygous as early as on day 106 at N3. The carrier males at the final generation were all fertile and propagated the modified genes. Thus, three congenic strains were established through rapid generation turnover between 41 and 44 days. CONCLUSIONS/SIGNIFICANCE: This new high-speed breeding strategy enables us to produce congenic strains within about half a year. It should provide the fastest protocol for precise definition of the phenotypic effects of genes of interest on desired genetic backgrounds