Epigenetic Regulation of the Nuclear and Mitochondrial Genomes: Involvement in Metabolism, Development, and Disease

Our understanding of the interactions between the nuclear and mitochondrial genomes is becoming increasingly important as they are extensively involved in establishing early development and developmental progression. Evidence from various biological systems indicates the interdependency between the genomes, which requires a high degree of compatibility and synchrony to ensure effective cellular function throughout development and in the resultant offspring. During development, waves of DNA demethylation, de novo methylation, and maintenance methylation act on the nuclear genome and typify oogenesis and pre- and postimplantation development. At the same time, significant changes in mitochondrial DNA copy number influence the metabolic status of the developing organism in a typically cell-type-specific manner. Collectively, at any given stage in development, these actions establish genomic balance that ensures each developmental milestone is met and that the organism's program for life is established.

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The genome of Populus alba x Populus tremula var. glandulosa clone 84K

DNA Research ◽

10.1093/dnares/dsz020 ◽

2019 ◽

Vol 26 (5) ◽

pp. 423-431 ◽

Cited By ~ 6

Author(s):

Deyou Qiu ◽

Shenglong Bai ◽

Jianchao Ma ◽

Lisha Zhang ◽

Fenjuan Shao ◽

...

Keyword(s):

De Novo ◽

Nuclear Genome ◽

Northern China ◽

Mitochondrial Genomes ◽

Populus Alba ◽

Sequencing Data ◽

High Quality ◽

Male Individual ◽

Poplar Hybrid ◽

Ecological Importance

AbstractPoplar 84K (Populus alba x P. tremula var. glandulosa) is a fast-growing poplar hybrid. Originated in South Korea, this hybrid has been extensively cultivated in northern China. Due to the economic and ecological importance of this hybrid and high transformability, we now report the de novo sequencing and assembly of a male individual of poplar 84K using PacBio and Hi-C technologies. The final reference nuclear genome (747.5 Mb) has a contig N50 size of 1.99 Mb and a scaffold N50 size of 19.6 Mb. Complete chloroplast and mitochondrial genomes were also assembled from the sequencing data. Based on similarities to the genomes of P. alba var. pyramidalis and P. tremula, we were able to identify two subgenomes, representing 356 Mb from P. alba (subgenome A) and 354 Mb from P. tremula var. glandulosa (subgenome G). The phased assembly allowed us to detect the transcriptional bias between the two subgenomes, and we found that the subgenome from P. tremula displayed dominant expression in both 84K and another widely used hybrid, P. tremula x P. alba. This high-quality poplar 84K genome will be a valuable resource for poplar breeding and for molecular biology studies.

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Cerebellotrigeminal Dermal Dysplasia (Gómez-López-Hernández Syndrome)

Journal of Pediatric Neurology ◽

10.1055/s-0038-1667021 ◽

2018 ◽

Vol 16 (05) ◽

pp. 362-368 ◽

Cited By ~ 1

Author(s):

Federica Sullo ◽

Agata Polizzi ◽

Stefano Catanzaro ◽

Selene Mantegna ◽

Francesco Lacarrubba ◽

...

Keyword(s):

De Novo ◽

Chromosomal Rearrangements ◽

Number Of Patients ◽

Wide Range ◽

Visual Problems ◽

Neurodevelopmental Abnormalities ◽

Clinical Triad ◽

High Degree ◽

Motor Handicap

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.

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Mitochondrial genome assembly v1

10.17504/protocols.io.bqzbmx2n ◽

2020 ◽

Author(s):

Graham Etherington

Keyword(s):

Mitochondrial Genome ◽

Genome Assembly ◽

De Novo Assembly ◽

De Novo ◽

Mitochondrial Genomes

De novo assembly of 49 mustelid whole mitochondrial genomes

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Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes

Journal of Experimental Medicine ◽

10.1084/jem.191.8.1281 ◽

2000 ◽

Vol 191 (8) ◽

pp. 1281-1292 ◽

Cited By ~ 146

Author(s):

Raelene J. Grumont ◽

Steve Gerondakis

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Nuclear Factor Κb ◽

Wild Type ◽

Cell Type ◽

Regulatory Factor ◽

Specific Manner ◽

A Cell ◽

Cell Type Specific ◽

Interferon Regulatory Factor 4

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel−/− B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel−/− B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor κB can repress the transcription of IFN-regulated genes in a cell type–specific manner.

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Discordant evolution of organellar genomes in peas (Pisum L.)

10.1101/2020.05.19.104224 ◽

2020 ◽

Cited By ~ 1

Author(s):

Vera S. Bogdanova ◽

Natalia V. Shatskaya ◽

Anatoliy V. Mglinets ◽

Oleg E. Kosterin ◽

Gennadiy V. Vasiliev

Keyword(s):

Phylogenetic Trees ◽

Nuclear Genome ◽

Nuclear Gene ◽

Plant Evolution ◽

Hybrid Origin ◽

Mitochondrial Genomes ◽

North East ◽

Plastid Genomes ◽

First Time ◽

Evolutionary Fate

AbstractPlastids and mitochondria have their own small genomes which do not undergo meiotic recombination and may have evolutionary fate different from each other and nuclear genome, thus highlighting interesting phenomena in plant evolution. We for the first time sequenced mitochondrial genomes of pea (Pisum L.), in 38 accessions mostly representing diverse wild germplasm from all over pea geographical range. Six structural types of pea mitochondrial genome were revealed. From the same accessions, plastid genomes were sequenced. Bayesian phylogenetic trees based on the plastid and mitochondrial genomes were compared. The topologies of these trees were highly discordant implying not less than six events of hybridisation of diverged wild peas in the past, with plastids and mitochondria differently inherited by the descendants. Such discordant inheritance of organelles is supposed to have been driven by plastid-nuclear incompatibility, known to be widespread in pea wide crosses and apparently shaping the organellar phylogenies. The topology of a phylogenetic tree based on the nucleotide sequence of a nuclear gene His5 coding for a histone H1 subtype corresponds to the current taxonomy and resembles that based on the plastid genome. Wild peas (Pisum sativum subsp. elatius s.l.) inhabiting Southern Europe were shown to be of hybrid origin resulting from crosses of peas similar to those presently inhabiting south-east and north-east Mediterranean in broad sense.

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Direct estimate of the spontaneous mutation rate uncovers the effects of drift and recombination in theChlamydomonas reinhardtiiplastid genome

10.1101/031898 ◽

2015 ◽

Author(s):

Rob W Ness ◽

Susanne A Kraemer ◽

Nick Colegrave ◽

Peter D Keightley

Keyword(s):

Mutation Rate ◽

Genetic Drift ◽

Plastid Genome ◽

De Novo ◽

Spontaneous Mutation ◽

Genome Structure ◽

Nuclear Genome ◽

De Novo Mutation ◽

Direct Estimate ◽

Plastid Genomes

Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input ofde novomutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation inChlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic dataset of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies inC. reinhardtiiand demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome.

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Site-specific methylation of adenine in the nuclear genome of a eucaryote, Tetrahymena thermophila.

Molecular and Cellular Biology ◽

10.1128/mcb.6.7.2364 ◽

1986 ◽

Vol 6 (7) ◽

pp. 2364-2370 ◽

Cited By ~ 23

Author(s):

G S Harrison ◽

R C Findly ◽

K M Karrer

Keyword(s):

Heat Shock ◽

Protein Gene ◽

De Novo ◽

Tetrahymena Thermophila ◽

Nuclear Genome ◽

Histone H4 ◽

Ciliated Protozoan ◽

Site Specific ◽

Logarithmic Growth ◽

I Gene

DNA in the polyploid macronucleus of the ciliated protozoan Tetrahymena thermophila contains the modified base N6-methyladenine. We identified two GATC sites which are methylated in most or all of the 45 copies of the macronuclear genome. One site is 2 kilobases 5' to the histone H4-I gene, and the other is 5 kilobases 3' to the 73-kilodalton heat shock protein gene. These sites are de novo methylated between 10 and 16 h after initiation of conjugation, during macronuclear anlage development. The methylation states of these two GATC sites and four other unmethylated GATC sites do not change in the DNA of cells cultured under conditions which change the activity of the genes, including logarithmic growth, starvation, and heat shock.

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TRIM28 maintains genome imprints and regulates development of porcine SCNT embryos

Reproduction ◽

10.1530/rep-20-0602 ◽

2021 ◽

Vol 161 (4) ◽

pp. 411-424

Author(s):

Yanhui Zhai ◽

Meng Zhang ◽

Xinglan An ◽

Sheng Zhang ◽

Xiangjie Kong ◽

...

Keyword(s):

Somatic Cell Nuclear Transfer ◽

Nuclear Transfer ◽

Transcript Abundance ◽

Dna Demethylation ◽

Epigenetic Variability ◽

Promoter Regions ◽

Cell Stage ◽

Genome Wide ◽

Developmental Progression ◽

Imprinting Gene

Pre-implantation embryos undergo genome-wide DNA demethylation, however certain regions, like imprinted loci remain methylated. Further, the mechanisms ensuring demethylation resistance by TRIM28 in epigenetic reprogramming remain poorly understood. Here, TRIM28 was knocked down in oocytes, and its effects on porcine somatic cell nuclear transfer (SCNT) embryo development was examined. Our results showed that SCNT embryos constructed from TRIM28 knockdown oocytes had significantly lower cleavage (53.9 ± 3.4% vs 64.8 ± 2.7%) and blastocyst rates (12.1 ± 4.3% vs 19.8 ± 1.9%) than control-SCNT embryos. The DNA methylation levels at the promoter regions of the imprinting gene IGF2 and H19 were significantly decreased in the 4-cell stage, and the transcript abundance of other imprinting gene was substantially increased. We also identified an aberrant two-fold decrease in the expression of CXXC1and H3K4me3 methyltransferase (ASH2L and MLL2), and the signal intensity of H3K4me3 had a transient drop in SCNT 2-cell embryos. Our results indicated that maternal TRIM28 knockdown disrupted the genome imprints and caused epigenetic variability in H3K4me3 levels, which blocked the transcription activity of zygote genes and affected the normal developmental progression of porcine SCNT embryos.

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De novo Assembly of the Brugia malayi Genome Using Long Reads from a Single MinION Flowcell

Scientific Reports ◽

10.1038/s41598-019-55908-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Joseph R. Fauver ◽

John Martin ◽

Gary J. Weil ◽

Makedonka Mitreva ◽

Peter U. Fischer

Keyword(s):

Single Molecule ◽

New Technologies ◽

Reference Genome ◽

De Novo ◽

Complete Mitochondrial Genome ◽

Nuclear Genome ◽

Brugia Malayi ◽

Field Isolates ◽

Sequencing Technologies ◽

Long Reads

AbstractFilarial nematode infections cause a substantial global disease burden. Genomic studies of filarial worms can improve our understanding of their biology and epidemiology. However, genomic information from field isolates is limited and available reference genomes are often discontinuous. Single molecule sequencing technologies can reduce the cost of genome sequencing and long reads produced from these devices can improve the contiguity and completeness of genome assemblies. In addition, these new technologies can make generation and analysis of large numbers of field isolates feasible. In this study, we assessed the performance of the Oxford Nanopore Technologies MinION for sequencing and assembling the genome of Brugia malayi, a human parasite widely used in filariasis research. Using data from a single MinION flowcell, a 90.3 Mb nuclear genome was assembled into 202 contigs with an N50 of 2.4 Mb. This assembly covered 96.9% of the well-defined B. malayi reference genome with 99.2% identity. The complete mitochondrial genome was obtained with individual reads and the nearly complete genome of the endosymbiotic bacteria Wolbachia was assembled alongside the nuclear genome. Long-read data from the MinION produced an assembly that approached the quality of a well-established reference genome using comparably fewer resources.

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