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Drosophila epigenetics

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https://www.readbyqxmd.com/read/28302795/causal-role-for-inheritance-of-h3k27me3-in-maintaining-the-off-state-of-a-drosophila-hox-gene
#1
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...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28302792/propagation-of-polycomb-repressed-chromatin-requires-sequence-specific-recruitment-to-dna
#2
Friederike Laprell, Katja Finkl, Jürg Müller
Epigenetic inheritance models posit that during Polycomb repression, Polycomb Repressive Complex 2 (PRC2) propagates histone H3K27 tri-methylation (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, whereas in replication-stalled cells, H3K27me3 levels stay high and repression persists...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28282384/adaptation-of-a-to-i-rna-editing-in-drosophila
#3
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
#4
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
#5
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28018141/what-drives-positive-selection-in-the-drosophila-pirna-machinery-the-genomic-autoimmunity-hypothesis
#12
REVIEW
Justin P Blumenstiel, Alexandra A Erwin, Lucas W Hemmer
In animals, PIWI-interacting RNAs (piRNAs) play a crucial role in genome defense. Moreover, because piRNAs can be maternally transmitted, they contribute to the epigenetic profile of inheritance. Multiple studies, especially in Drosophila, have demonstrated that the machinery of piRNA biogenesis is often the target of positive selection. Because transposable elements (TEs) are a form of genetic parasite, positive selection in the piRNA machinery is often explained by analogy to the signatures of positive selection commonly observed in genes that play a role in host-parasite dynamics...
December 2016: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/27932388/from-embryo-to-adult-pirna-mediated-silencing-throughout-germline-development-in-drosophila
#13
Pauline P Marie, Stéphane Ronsseray, Antoine Boivin
In metazoan germ cells, transposable element activity is repressed by small noncoding PIWI-associated RNAs (piRNAs). Numerous studies in Drosophila have elucidated the mechanism of this repression in the adult germline. However, when and how transposable element repression is established during germline development, has not been addressed. Here, we show that homology-dependent trans silencing is active in female primordial germ cells from late embryogenesis through pupal stages, and that genes related to the adult piRNA pathway are required for silencing during development...
December 14, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27924023/methsmrt-an-integrative-database-for-dna-n6-methyladenine-and-n4-methylcytosine-generated-by-single-molecular-real-time-sequencing
#14
Pohao Ye, Yizhao Luan, Kaining Chen, Yizhi Liu, Chuanle Xiao, Zhi Xie
DNA methylation is an important type of epigenetic modifications, where 5- methylcytosine (5mC), 6-methyadenine (6mA) and 4-methylcytosine (4mC) are the most common types. Previous efforts have been largely focused on 5mC, providing invaluable insights into epigenetic regulation through DNA methylation. Recently developed single-molecule real-time (SMRT) sequencing technology provides a unique opportunity to detect the less studied DNA 6mA and 4mC modifications at single-nucleotide resolution. With a rapidly increased amount of SMRT sequencing data generated, there is an emerging demand to systematically explore DNA 6mA and 4mC modifications from these data sets...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27907135/the-histone-deacetylase-gene-rpd3-is-required-for-starvation-stress-resistance
#15
Ei Nakajima, Kouhei Shimaji, Takanari Umegawachi, Saki Tomida, Hideki Yoshida, Nana Yoshimoto, Shingo Izawa, Hiroshi Kimura, Masamitsu Yamaguchi
Epigenetic regulation in starvation is important but not fully understood yet. Here we identified the Rpd3 gene, a Drosophila homolog of histone deacetylase 1, as a critical epigenetic regulator for acquiring starvation stress resistance. Immunostaining analyses of Drosophila fat body revealed that the subcellular localization and levels of Rpd3 dynamically changed responding to starvation stress. In response to starvation stress, the level of Rpd3 rapidly increased, and it accumulated in the nucleolus in what appeared to be foci...
2016: PloS One
https://www.readbyqxmd.com/read/27889707/transgenerational-programming-of-longevity-through-e-z-mediated-histone-h3k27-trimethylation-in-drosophila
#16
Brian Xia, Ed Gerstin, Dustin E Schones, Wendong Huang, J Steven de Belle
Transgenerational effects on health and development of early-life nutrition have gained increased attention recently. However, the underlying mechanisms of transgenerational transmission are only starting to emerge, with epigenetics as perhaps the most important mechanism. We recently reported the first animal model to study transgenerational programming of longevity after early-life dietary manipulations, enabling investigations to identify underlying epigenetic mechanisms. We report here that post-eclosion dietary manipulation (PDM) with a low-protein (LP) diet upregulates the protein level of E(z), an H3K27 specific methyltransferase, leading to higher levels of H3K27 trimethylation (H3K27me3)...
November 25, 2016: Aging
https://www.readbyqxmd.com/read/27880074/what-does-the-fruitless-gene-tell-us-about-nature-vs-nurture-in-the-sex-life-of-drosophila
#17
Daisuke Yamamoto, Soh Kohatsu
The fruitless (fru) gene in Drosophila has been proposed to play a master regulator role in the formation of neural circuitries for male courtship behavior, which is typically considered to be an innate behavior composed of a fixed action pattern as generated by the central pattern generator. However, recent studies have shed light on experience-dependent changes and sensory-input-guided plasticity in courtship behavior. For example, enhanced male-male courtship, a fru mutant "hallmark," disappears when fru-mutant males are raised in isolation...
November 23, 2016: Fly
https://www.readbyqxmd.com/read/27866148/identification-of-genes-mediating-drosophila-follicle-cell-progenitor-differentiation-by-screening-for-modifiers-of-gal4-uas-variegation
#18
Ming-Chia Lee, Andrew D Skora, Allan C Spradling
The Drosophila melanogaster ovarian follicle cell lineage provides a powerful system for investigating how epigenetic changes contribute to differentiation. Downstream from an epithelial stem cell, follicle progenitors undergo nine mitotic cell cycles before transitioning to the endocycle and initiating differentiation. During their proliferative phase, follicle progenitors experience Lsd1-dependent changes in epigenetic stability that can be monitored using GAL4::UAS variegation. Eventually, follicle progenitors acquire competence to respond to Delta, a Notch ligand present in the environment, which signals them to cease division and initiate differentiation...
January 5, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27858939/chromatin-remodeling-during-in-vivo-neural-stem-cells-differentiating-to-neurons-in-early-drosophila-embryos
#19
Youqiong Ye, Min Li, Liang Gu, Xiaolong Chen, Jiejun Shi, Xiaobai Zhang, Cizhong Jiang
Neurons are a key component of the nervous system and differentiate from multipotent neural stem cells (NSCs). Chromatin remodeling has a critical role in the differentiation process. However, its in vivo epigenetic regulatory role remains unknown. We show here that nucleosome depletion regions (NDRs) form in both proximal promoters and distal enhancers during NSCs differentiating into neurons in the early Drosophila embryonic development. NDR formation in the regulatory regions involves nucleosome shift and eviction...
March 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27856695/multiplex-shrna-screening-of-germ-cell-development-by-in-vivo-transfection-of-mouse-testis
#20
Nicholas R Y Ho, Abul R Usmani, Yan Yin, Liang Ma, Donald F Conrad
Spermatozoa are one of the few mammalian cell types that cannot be fully derived in vitro, severely limiting the application of modern genomic techniques to study germ cell biology. The current gold standard approach of characterizing single-gene knockout mice is slow as generation of each mutant line can take 6-9 months. Here, we describe an in vivo approach to rapid functional screening of germline genes based on a new nonsurgical, nonviral in vivo transfection method to deliver nucleic acids into testicular germ cells...
January 5, 2017: G3: Genes—Genomes—Genetics
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