Advances in Breeding of Peach, Plum and Apricot

Research on the expression of fruit specific genes may allow breeders in the future to selectively manipulate through gene transfer in certain aspects of fruit development/quality in their advanced breeding lines thus reducing the time necessary for cultivar development. This would be particularly useful in breeding programmes, hybridizing standard cultivars with exotic germplasm of low fruit quality. The use of exotic germplasm will be important for the expansion of the peach germplasm base and the development of stress resistant cultivars. More immediate results of research on fruit specific gene expression will provide a better understanding of fruit development and quality. It is required to learn how the differences at the gene level correlate with quality characteristics. With the continued cooperation of fruit biochemists it is expected to obtain a better definition of fruit quality and a better understanding of fruit biochemistry. The potential will exit to generate a range of “anti-sense mutants” i.e. transgenic plants expressing anti-sense gene contstructs that reduce or nullify the effects of the normal gene. The phenotypes of these mutants could help to define the biochemistry, genetics and quality of peach fruit. The development of efficient regeneration and transformation system in peach will be useful not only for the modification of fruit characteristics, but also for the transfer and manipulation of genes affecting stress resistance and other economically important characters.

SIRT7: a sentinel of genome stability

SIRT7 is a class III histone deacetylase that belongs to the sirtuin family. The past two decades have seen numerous breakthroughs in terms of understanding SIRT7 biological function. We now know that this enzyme is involved in diverse cellular processes, ranging from gene regulation to genome stability, ageing and tumorigenesis. Genomic instability is one hallmark of cancer and ageing; it occurs as a result of excessive DNA damage. To counteract such instability, cells have evolved a sophisticated regulated DNA damage response mechanism that restores normal gene function. SIRT7 seems to have a critical role in this response, and it is recruited to sites of DNA damage where it recruits downstream repair factors and directs chromatin regulation. In this review, we provide an overview of the role of SIRT7 in DNA repair and maintaining genome stability. We pay particular attention to the implications of SIRT7 function in cancer and ageing.

Topologically Associating Domain Boundaries are Commonly Required for Normal Genome Function

Topologically associating domain (TAD) boundaries are thought to partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotype, but the overall extent to which this occurs remains unknown. Here we show that TAD boundary deletions commonly disrupt normal genome function in vivo. We used CRISPR genome editing in mice to individually delete eight TAD boundaries (11-80kb in size) from the genome in mice. All deletions examined resulted in at least one detectable molecular or organismal phenotype, which included altered chromatin interactions or gene expression, reduced viability, and anatomical phenotypes. For 5 of 8 (62%) loci examined, boundary deletions were associated with increased embryonic lethality or other developmental phenotypes. For example, a TAD boundary deletion near Smad3/Smad6 caused complete embryonic lethality, while a deletion near Tbx5/Lhx5 resulted in a severe lung malformation. Our findings demonstrate the importance of TAD boundary sequences for in vivo genome function and suggest that noncoding deletions affecting TAD boundaries should be carefully considered for potential pathogenicity in clinical genetics screening.

A conserved role for the ALS-linked splicing factor SFPQ in repression of pathogenic cryptic last exons

The RNA-binding protein SFPQ plays an important role in neuronal development and has been associated with several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease. Here, we report that loss of sfpq leads to premature termination of multiple transcripts due to widespread activation of previously unannotated cryptic last exons (CLEs). These SFPQ-inhibited CLEs appear preferentially in long introns of genes with neuronal functions and can dampen gene expression outputs and/or give rise to short peptides interfering with the normal gene functions. We show that one such peptide encoded by the CLE-containing epha4b mRNA isoform is responsible for neurodevelopmental defects in the sfpq mutant. The uncovered CLE-repressive activity of SFPQ is conserved in mouse and human, and SFPQ-inhibited CLEs are found expressed across ALS iPSC-derived neurons. These results greatly expand our understanding of SFPQ function and uncover a gene regulation mechanism with wide relevance to human neuropathologies.

Overcoming the problem of the lack of an immune response to cancer: A possible haptogenic approach to cancer immunotherapy

Cancer cells possess a number of unusual features, most of which are explicable in the light of the theory of epigenetic carcinogenesis. This includes the remarkable failure of malignant cells to evoke an immunological response from the host which is ascribed to their deviant behaviour resulting from anomalous expression of normal gene products. Given this background a possible approach to eliciting a specific anti-cancer immune response is proposed which involves selective haptenation of an identifiable target protein.

Copper-free and enzyme-free click chemistry-mediated single quantum dot nanosensor for accurate detection of microRNAs in cancer cells and tissues

MicroRNAs (miRNAs) play key roles in the post-transcriptional regulation of genes, and their aberrant expression may disturb the normal gene regulation network to induce various diseases, and thus accurate detection...

Physiological Changes in Barley mlo-11 Powdery Mildew Resistance Conditioned by Tandem Repeat Copy Number

Wild barley accessions have evolved broad-spectrum defence against barley powdery mildew through recessive mlo mutations. However, the mlo defence response is associated with deleterious phenotypes with a cost to yield and fertility, with implications for natural fitness and agricultural productivity. This research elucidates the mechanism behind a novel mlo allele, designated mlo-11(cnv2), which has a milder phenotype compared to standard mlo-11. Bisulphite sequencing and histone ChIP-seq analyses using near-isogenic lines showed pronounced repression of the Mlo promoter in standard mlo-11 compared to mlo-11(cnv2), with repression governed by 24 nt heterochromatic small interfering RNAs. The mlo-11(cnv2) allele appears to largely reduce the physiological effects of mlo while still endorsing a high level of powdery mildew resistance. RNA sequencing showed that this is achieved through only partly restricted expression of Mlo, allowing adequate temporal induction of defence genes during infection and expression close to wild-type Mlo levels in the absence of infection. The two mlo-11 alleles showed copy number proportionate oxidase and peroxidase expression levels during infection, but lower amino acid and aromatic compound biosynthesis compared to the null allele mlo-5. Examination of highly expressed genes revealed a common WRKY W-box binding motif (consensus ACCCGGGACTAAAGG) and a transcription factor more highly expressed in mlo-11 resistance. In conclusion, mlo-11(cnv2) appears to significantly mitigate the trade-off between mlo defence and normal gene expression.

Dietary restriction and/or exercise training impairs spermatogenesis in normal rats

Dietary restriction and/or exercise has been shown to have multiple benefits for health. However, its effects on reproductive health and the mechanisms by which it regulates reproductive function remain unclear. Here, in order to evaluate its effects on spermatogenesis and sperm function, rats were divided into four groups: ad libitum-fed sedentary control (CO), dietary restriction (DR), exercise training (ET), and dietary restriction plus exercise training (DR+ET) groups. Results indicated that body weight, epididymal fat pad weight, and sperm counts were significantly reduced in the DR, ET, and DR+ET groups. Moreover, sperm motility and capacitation-associated protein tyrosine phosphorylation were suppressed in the DR and DR+ET groups, but not the ET group. Microarray analysis revealed that the number of downregulated genes was higher than that of upregulated genes in the DR and/or ET groups. About half of the downregulated genes are common after exercise training and/or diet restriction. Gene ontology analysis showed that downregulated genes in the DR, ET, and DR+ET groups affected spermatogenesis through overlapping pathways, including glucocorticoid, corticosteroid, extracellular structure organization, and estradiol responses. Our findings suggest that diet restriction and/or exercise training may present potential risks to male reproductive dysfunction by disrupting normal gene expression patterns in the testis. Novelty bullets: 1. Dietary restriction and/or exercise can lead to the damage of spermatogenesis as well as sperm maturation. 2. Sperm functional changes are more sensitive to dietary restriction than exercise training. 3. Dietary restriction and exercise impair spermatogenesis through overlapping biological pathways in the testis.

Chromatin profiling reveals reorganization of lysine specific demethylase 1 by an oncogenic fusion protein

ABSTRACTPediatric cancers commonly harbor quiet mutational landscapes and are instead characterized by single driver events such as the mutation of critical chromatin regulators, expression of oncohistones, or expression of oncogenic fusion proteins. These events ultimately promote malignancy through disruption of normal gene regulation and development. The driver protein in Ewing sarcoma, EWS/FLI, is an oncogenic fusion and transcription factor that reshapes the enhancer landscape, resulting in widespread transcriptional dysregulation. Lysine-specific demethylase 1 (LSD1) is a critical functional partner for EWS/FLI as inhibition of LSD1 reverses the transcriptional activity of EWS/FLI. However, how LSD1 participates in fusion-directed epigenomic regulation and aberrant gene activation is unknown. We now show EWS/FLI causes dynamic rearrangement of LSD1 and we uncover a role for LSD1 in gene activation through colocalization at EWS/FLI binding sites throughout the genome. LSD1 is integral to the establishment of Ewing sarcoma super-enhancers at GGAA-microsatellites, which ubiquitously overlap non-microsatellite loci bound by EWS/FLI. Together, we show that EWS/FLI induces widespread changes to LSD1 distribution in a process that impacts the enhancer landscape throughout the genome.

A conserved role for SFPQ in repression of pathogenic cryptic last exons

The RNA-binding protein SFPQ plays an important role in neuronal development and has been associated with several neurodegenerative disorders, including ALS, FTLD, and Alzheimer’s Disease. Here, we report that loss of sfpq leads to premature termination of multiple transcripts due to widespread activation of previously unannotated cryptic last exons (CLEs). These CLEs appear preferentially in long introns of genes with neuronal functions and dampen gene expression outputs and/or give rise to short peptides interfering with the normal gene functions. We show that one such peptide encoded by the CLE-containing epha4b mRNA isoform is responsible for neurodevelopmental defects in the sfpq mutant. The uncovered CLE-repressive activity of SFPQ is conserved in mouse and human, and SFPQ-inhibited CLEs are found across ALS iPSC-derived neurons. These results greatly expand our understanding of SFPQ function and uncover a new gene regulation mechanism with wide relevance to human pathologies.