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Drosophila epigenetics

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https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#1
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28515049/a-generalized-linear-model-for-decomposing-cis-regulatory-parent-of-origin-and-maternal-effects-on-allele-specific-gene-expression
#2
Yasuaki Takada, Ryutaro Miyagi, Aya Takahashi, Toshinori Endo, Naoki Osada
Joint quantification of genetic and epigenetic effects on gene expression is important for understanding the establishment of complex gene regulation systems in living organisms. In particular, genomic imprinting and maternal effects play important roles in the developmental process of mammals and flowering plants. However, the influence of these effects on gene expression are difficult to quantify because they act simultaneously with cis-regulatory mutations. Here we propose a simple method to decompose cis-regulatory (i...
May 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28465421/hyperactive-locomotion-in-a-drosophila-model-is-a-functional-readout-for-the-synaptic-abnormalities-underlying-fragile-x-syndrome
#3
Risa Kashima, Patrick L Redmond, Prajakta Ghatpande, Sougata Roy, Thomas B Kornberg, Thomas Hanke, Stefan Knapp, Giorgio Lagna, Akiko Hata
Fragile X syndrome (FXS) is the most common cause of heritable intellectual disability and autism and affects ~1 in 4000 males and 1 in 8000 females. The discovery of effective treatments for FXS has been hampered by the lack of effective animal models and phenotypic readouts for drug screening. FXS ensues from the epigenetic silencing or loss-of-function mutation of the fragile X mental retardation 1 (FMR1) gene, which encodes an RNA binding protein that associates with and represses the translation of target mRNAs...
May 2, 2017: Science Signaling
https://www.readbyqxmd.com/read/28457744/piwi-is-required-during-drosophila-embryogenesis-to-license-dual-strand-pirna-clusters-for-transposon-repression-in-adult-ovaries
#4
Abdou Akkouche, Bruno Mugat, Bridlin Barckmann, Carolina Varela-Chavez, Blaise Li, Raoul Raffel, Alain Pélisson, Séverine Chambeyron
Most piRNAs in the Drosophila female germline are transcribed from heterochromatic regions called dual-strand piRNA clusters. Histone 3 lysine 9 trimethylation (H3K9me3) is required for licensing piRNA production by these clusters. However, it is unclear when and how they acquire this permissive heterochromatic state. Here, we show that transient Piwi depletion in Drosophila embryos results in H3K9me3 decrease at piRNA clusters in ovaries. This is accompanied by impaired biogenesis of ovarian piRNAs, accumulation of transposable element transcripts, and female sterility...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28449092/genome-wide-dna-methylomes-from-discrete-developmental-stages-reveal-the-predominance-of-non-cpg-methylation-in-tribolium-castaneum
#5
Xiaowen Song, Fei Huang, Juanjuan Liu, Chengjun Li, Shanshan Gao, Wei Wu, Mengfan Zhai, Xiaojuan Yu, Wenfeng Xiong, Jia Xie, Bin Li
Cytosine DNA methylation is a vital epigenetic regulator of eukaryotic development. Whether this epigenetic modification occurs in Tribolium castaneum has been controversial, its distribution pattern and functions have not been established. Here, using bisulphite sequencing (BS-Seq), we confirmed the existence of DNA methylation and described the methylation profiles of the four life stages of T. castaneum. In the T. castaneum genome, both symmetrical CpG and non-CpG methylcytosines were observed. Symmetrical CpG methylation, which was catalysed by DNMT1 and occupied a small part in T...
April 25, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28442993/alcohol-induced-neuroadaptation-is-orchestrated-by-the-histone-acetyltransferase-cbp
#6
Alfredo Ghezzi, Xiaolei Li, Linda K Lew, Thilini P Wijesekera, Nigel S Atkinson
Homeostatic neural adaptations to alcohol underlie the production of alcohol tolerance and the associated symptoms of withdrawal. These adaptations have been shown to persist for relatively long periods of time and are believed to be of central importance in promoting the addictive state. In Drosophila, a single exposure to alcohol results in long-lasting alcohol tolerance and symptoms of withdrawal following alcohol clearance. These persistent adaptations involve mechanisms such as long-lasting changes in gene expression and perhaps epigenetic restructuring of chromosomal regions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28436983/stable-polycomb-dependent-transgenerational-inheritance-of-chromatin-states-in-drosophila
#7
Filippo Ciabrelli, Federico Comoglio, Simon Fellous, Boyan Bonev, Maria Ninova, Quentin Szabo, Anne Xuéreb, Christophe Klopp, Alexei Aravin, Renato Paro, Frédéric Bantignies, Giacomo Cavalli
Transgenerational epigenetic inheritance (TEI) describes the transmission of alternative functional states through multiple generations in the presence of the same genomic DNA sequence. Very little is known about the principles and the molecular mechanisms governing this type of inheritance. Here, by transiently enhancing 3D chromatin interactions, we established stable and isogenic Drosophila epilines that carry alternative epialleles, as defined by differential levels of Polycomb-dependent trimethylation of histone H3 Lys27 (forming H3K27me3)...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28374742/the-histone-methyltransferase-ash1l-is-required-for-epidermal-homeostasis-in-mice
#8
Gang Li, Zhisheng Ye, Cheng Shi, Ling Sun, Min Han, Yuan Zhuang, Tian Xu, Shimin Zhao, Xiaohui Wu
Epidermal homeostasis under normal and healing conditions are critical for the physical and functional maintenance of the skin barrier. It requires a proper balance between keratinocyte proliferation and differentiation under genetic and epigenetic regulations. Here we show that mice carrying a hypomorphic mutation of the histone methyltransferase Ash1l [(absent, small, or homeotic)-like (Drosophila)] develop epidermal hyperplasia and impaired epidermal stratification upon aging. In adult mutants, loss of Ash1l leads to more proliferative keratinocytes in disturbed differentiation stages...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28355214/a-new-paramutation-like-example-at-the-delta-gene-of-drosophila
#9
Maria Capovilla, Alain Robichon, Minoo Rassoulzadegan
The hereditary transmission of a phenotype independent from DNA sequence implies epigenetic effects. Paramutation is a heritable epigenetic phenomenon observed in plants and animals. To investigate paramutation in Drosophila, we used the P{ry+t7.2 = PZ}Dl05151 P-element insertion in the Drosophila melanogaster genome that causes a dominant visible phenotype: the presence of characteristic extra-veins in the fly wings. This extra-vein phenotype presents variable expressivity and incomplete penetrance. The insert is a PZ element located 680 bp upstream from the ATG of the Delta (Dl) gene, encoding the Notch ligand involved in wing vein development, and acts as a null allele...
2017: PloS One
https://www.readbyqxmd.com/read/28302795/causal-role-for-inheritance-of-h3k27me3-in-maintaining-the-off-state-of-a-drosophila-hox-gene
#10
Rory T Coleman, Gary Struhl
Many eukaryotic cells can respond to transient environmental or developmental stimuli with heritable changes in gene expression that are associated with nucleosome modifications. However, it remains uncertain whether modified nucleosomes play a causal role in transmitting such epigenetic memories, as opposed to controlling or merely reflecting transcriptional states inherited by other means. Here, we provide in vivo evidence that H3K27 trimethylated nucleosomes, once established at a repressed Drosophila HOX gene, remain heritably associated with that gene and can carry the memory of the silenced state through multiple rounds of replication, even when the capacity to copy the H3K27me3 mark to newly incorporated nucleosomes is diminished or abolished...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28302792/propagation-of-polycomb-repressed-chromatin-requires-sequence-specific-recruitment-to-dna
#11
Friederike Laprell, Katja Finkl, Jürg Müller
Epigenetic inheritance models posit that during Polycomb repression, Polycomb repressive complex 2 (PRC2) propagates histone H3 lysine 27 trimethylation (H3K27me3) independently of DNA sequence. We show that insertion of Polycomb response element (PRE) DNA into the Drosophila genome creates extended domains of H3K27me3-modified nucleosomes in the flanking chromatin and causes repression of a linked reporter gene. After excision of PRE DNA, H3K27me3 nucleosomes become diluted with each round of DNA replication, and reporter gene repression is lost...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28282384/adaptation-of-a-to-i-rna-editing-in-drosophila
#12
Yuange Duan, Shengqian Dou, Shiqi Luo, Hong Zhang, Jian Lu
Adenosine-to-inosine (A-to-I) editing is hypothesized to facilitate adaptive evolution by expanding proteomic diversity through an epigenetic approach. However, it is challenging to provide evidences to support this hypothesis at the whole editome level. In this study, we systematically characterized 2,114 A-to-I RNA editing sites in female and male brains of D. melanogaster, and nearly half of these sites had events evolutionarily conserved across Drosophila species. We detected strong signatures of positive selection on the nonsynonymous editing sites in Drosophila brains, and the beneficial editing sites were significantly enriched in genes related to chemical and electrical neurotransmission...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28247044/role-of-chromatin-modifications-in-drosophila-germline-stem-cell-differentiation
#13
Pooja Flora, Alicia McCarthy, Maitreyi Upadhyay, Prashanth Rangan
During Drosophila oogenesis, germline stem cells (GSCs) self-renew and differentiate to give rise to a mature egg. Self-renewal and differentiation of GSCs are regulated by both intrinsic mechanisms such as regulation of gene expression in the germ line and extrinsic signaling pathways from the surrounding somatic niche. Epigenetic mechanisms, including histone-modifying proteins, nucleosome remodeling complexes, and histone variants, play a critical role in regulating intrinsic gene expression and extrinsic signaling cues from the somatic niche...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#14
REVIEW
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. Although much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act posttranscriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBP) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
May 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28137283/the-hunchback-temporal-transcription-factor-establishes-but-is-not-required-to-maintain-early-born-neuronal-identity
#15
Keiko Hirono, Minoree Kohwi, Matt Q Clark, Ellie S Heckscher, Chris Q Doe
BACKGROUND: Drosophila and mammalian neural progenitors typically generate a diverse family of neurons in a stereotyped order. Neuronal diversity can be generated by the sequential expression of temporal transcription factors. In Drosophila, neural progenitors (neuroblasts) sequentially express the temporal transcription factors Hunchback (Hb), Kruppel, Pdm, and Castor. Hb is necessary and sufficient to specify early-born neuronal identity in multiple lineages, and is maintained in the post-mitotic neurons produced during each neuroblast expression window...
January 31, 2017: Neural Development
https://www.readbyqxmd.com/read/28115720/drosophila-larvae-synthesize-the-putative-oncometabolite-l-2-hydroxyglutarate-during-normal-developmental-growth
#16
Hongde Li, Geetanjali Chawla, Alexander J Hurlburt, Maria C Sterrett, Olga Zaslaver, James Cox, Jonathan A Karty, Adam P Rosebrock, Amy A Caudy, Jason M Tennessen
L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094282/evidence-of-neofunctionalization-after-the-duplication-of-the-highly-conserved-polycomb-group-gene-caf1-55-in-the-obscura-group-of-drosophila
#17
Juan M Calvo-Martín, Montserrat Papaceit, Carmen Segarra
Drosophila CAF1-55 protein is a subunit of the Polycomb repressive complex PRC2 and other protein complexes. It is a multifunctional and evolutionarily conserved protein that participates in nucleosome assembly and remodelling, as well as in the epigenetic regulation of a large set of target genes. Here, we describe and analyze the duplication of Caf1-55 in the obscura group of Drosophila. Paralogs exhibited a strong asymmetry in evolutionary rates, which suggests that they have evolved according to a neofunctionalization process...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28076775/nutritional-programming-of-lifespan-by-foxo-inhibition-on-sugar-rich-diets
#18
Adam J Dobson, Marina Ezcurra, Charlotte E Flanagan, Adam C Summerfield, Matthew D W Piper, David Gems, Nazif Alic
Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO-the Drosophila homolog of forkhead box O (FOXO) transcription factors-and represses expression of dFOXO target genes encoding epigenetic regulators...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28048969/on-the-developmental-self-regulatory-dynamics-and-evolution-of-individuated-multicellular-organisms
#19
Felipe A Veloso
Changes in gene expression are thought to regulate the cell differentiation process intrinsically through complex epigenetic mechanisms. In fundamental terms, however, this assumed regulation refers only to the intricate propagation of changes in gene expression or else leads to non-explanatory regresses. The developmental self-regulatory dynamics and evolution of individuated multicellular organisms also lack a unified and falsifiable description. To fill this gap, I computationally analyzed publicly available high-throughput data of histone H3 post-translational modifications and mRNA abundance for different Homo sapiens, Mus musculus, and Drosophila melanogaster cell-type/developmental-period samples...
December 31, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28028175/the-transcriptional-corepressor-sin3-directly-regulates-genes-involved-in-methionine-catabolism-and-affects-histone-methylation-linking-epigenetics-and-metabolism
#20
Mengying Liu, Lori A Pile
Chromatin modification and cellular metabolism are tightly connected. Chromatin modifiers regulate the expression of genes involved in metabolism and, in turn, the levels of metabolites. The generated metabolites are utilized by chromatin modifiers to affect epigenetic modification. The mechanism for this cross-talk, however, remains incompletely understood. The corepressor SIN3 controls histone acetylation through association with the histone deacetylase RPD3. The SIN3 complex is known to regulate genes involved in a number of metabolic processes...
February 3, 2017: Journal of Biological Chemistry
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