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Drosophila epigenetics

Lore Becker, Melanie Schmitt Nogueira, Caroline Klima, Martin Hrabe de Angelis, Shahaf Peleg
Epigenetic deregulation, such as the reduction of histone acetylation levels, is thought to be causally linked to various maladies associated with aging. Consequently, histone deacetylase inhibitors are suggested to serve as epigenetic therapy by increasing histone acetylation. However, previous work suggests that many non-histone proteins, including metabolic enzymes, are also acetylated and that post transitional modifications may impact their activity. Furthermore, deacetylase inhibitors were recently shown to impact the acetylation of a variety of proteins...
March 8, 2018: Scientific Reports
Quentin Szabo, Daniel Jost, Jia-Ming Chang, Diego I Cattoni, Giorgio L Papadopoulos, Boyan Bonev, Tom Sexton, Julian Gurgo, Caroline Jacquier, Marcelo Nollmann, Frédéric Bantignies, Giacomo Cavalli
Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear...
February 2018: Science Advances
Amy J Osborne, Peter K Dearden
The Developmental Origins of Health and Disease hypothesis predicts that early-life environmental exposures can be detrimental to later-life health and that mismatch between the pre- and post-natal environment may contribute to the growing non-communicable disease epidemic. Within this is an increasingly recognized role for epigenetic mechanisms; for example, epigenetic modifications can be influenced by nutrition and can alter gene expression in mothers and offspring. Currently, there are few whole-genome transcriptional studies of response to nutritional alteration...
October 2017: Environmental Epigenetics
Ana García Del Arco, Bruce A Edgar, Sylvia Erhardt
Stem cells of the Drosophila midgut (ISCs) are the only mitotically dividing cells of the epithelium and, therefore, presumably the only epithelial cells that require functional kinetochores for microtubule spindle attachment during mitosis. The histone variant CENP-A marks centromeric chromatin as the site of kinetochore formation and spindle attachment during mitotic chromosome segregation. Here, we show that centromeric proteins distribute asymmetrically during ISC division. Whereas newly synthesized CENP-A is enriched in differentiating progeny, CENP-C is undetectable in these cells...
February 20, 2018: Cell Reports
Parna Saha, Divya Tej Sowpati, Rakesh K Mishra
Heterochromatin is associated with transcriptional repression. In contrast, several genes in the pericentromeric regions of Drosophila melanogaster are dependent on this heterochromatic environment for their expression. Here we present a comprehensive analysis of the epigenetic landscape of heterochromatic genes across all the developmental stages of Drosophila using the available histone modification and expression data from modENCODE. We find that heterochromatic genes exhibit combinations of active and inactive histone marks that correspond to their level of expression during development...
February 9, 2018: Genomics
Ting Lian, Uma Gaur, Q I Wu, Jianbo Tu, Boyuan Sun, Deying Yang, Xiaolan Fan, Xueping Mao, Mingyao Yang
Dietary restriction (DR) is widely regarded as a viable intervention to extend lifespan and healthspan in diverse organisms. The precise molecular regulatory mechanisms are largely unknown. Epigenetic modifications are not stable upon DR and also keep changing with age. Here, we employed whole genome bisulfite sequencing to determine the DNA methylation changes upon DR in adult Drosophila. Our results indicate that although a low level of DNA methylation exists in the adult Drosophila genome, there is no significant difference in DNA methylation levels upon DR when compared to unrestricted flies...
February 1, 2018: Genetics Research
D A Chetverina, P V Elizar’ev, D V Lomaev, P G Georgiev, M M Erokhin
Combinatorial expression of the genes in multicellular organisms leads to the development of different cell types. The important epigenetic regulators of higher eukaryotes are the Polycomb group (PcG) and Trithorax group (TrxG) proteins. These factors control the transcription of a large number of genes involved in various cellular processes. Dysregulation of PcG and TrxG systems leads to developmental abnormalities and cancer. This review focuses on the main characteristics and properties of the Drosophila PRE elements...
February 2017: Genetika
Qicong Shen, Qian Zhang, Yang Shi, Qingzhu Shi, Yanyan Jiang, Yan Gu, Zhiqing Li, Xia Li, Kai Zhao, Chunmei Wang, Nan Li, Xuetao Cao
Varieties of RNA modification form the epitranscriptome for post-transcriptional regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA (mRNA) under physiological conditions. The function of RNA 5-hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins in Drosophila has been revealed more recently. However, the turnover and function of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid malignancies mostly in an enzymatic activity-dependent manner, and is important in resolving inflammatory response in an enzymatic activity-independent way...
February 1, 2018: Nature
Nicholas Allen Kinney, Igor V Sharakhov, Alexey V Onufriev
BACKGROUND: It is well recognized that the interphase chromatin of higher eukaryotes folds into non-random configurations forming territories within the nucleus. Chromosome territories have biologically significant properties, and understanding how these properties change with time during lifetime of the cell is important. Chromosome-nuclear envelope (Chr-NE) interactions play a role in epigenetic regulation of DNA replication, repair, and transcription. However, their role in maintaining chromosome territories remains unclear...
January 22, 2018: Epigenetics & Chromatin
Elizabeth W Kahney, Rajesh Ranjan, Ryan J Gleason, Xin Chen
The processes of DNA replication and mitosis allow the genetic information of a cell to be copied and transferred reliably to its daughter cells. However, if DNA replication and cell division were always performed in a symmetric manner, the result would be a cluster of tumor cells instead of a multicellular organism. Therefore, gaining a complete understanding of any complex living organism depends on learning how cells become different while faithfully maintaining the same genetic material. It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
Isabel Fast, David Rosenkranz
Temperature has a major impact on gene expression in ectotherms. But until recently, it was not clear in which way, if any, small non-coding RNAs such as miRNAs or piRNAs contribute to thermosensitive gene regulation. We have recently shown that temperature-responsive miRNAs in Drosophila drive adaptation to different ambient temperatures on the transcriptome level. Moreover, we demonstrated that higher temperatures lead to a more efficient piRNA-dependent transposon silencing, possibly due to heat-induced unfolding of RNA secondary structures...
January 18, 2018: RNA Biology
Nina K Latcheva, Jennifer M Viveiros, Edward A Waddell, Phuong T T Nguyen, Faith L W Liebl, Daniel R Marenda
We are beginning to appreciate the complex mechanisms by which epigenetic proteins control chromatin dynamics to tightly regulate normal development. However, the interaction between these proteins, particularly in the context of neuronal function, remains poorly understood. Here, we demonstrate that the activity of histone deacetylases (HDACs) opposes that of a chromatin remodeling enzyme at the Drosophila neuromuscular junction (NMJ). Pharmacological inhibition of HDAC function reverses loss of function phenotypes associated with Kismet, a chromodomain helicase DNA-binding (CHD) protein...
December 14, 2017: Molecular and Cellular Neurosciences
Liangjun Wang, Preeti Joshi, Ellen L Miller, LeeAnn Higgins, Matthew Slattery, Jeffrey A Simon
Polycomb repressive complex 2 (PRC2) is a conserved chromatin-modifying enzyme that methylates histone H3 on lysine-27 (K27).  PRC2 can add one, two, or three methyl groups and the fully methylated product, H3-K27me3, is a hallmark of Polycomb-silenced chromatin.  Less is known about functions of K27me1 and K27me2 and the dynamics of flux through these states.  These modifications could serve mainly as intermediates to produce K27me3 or they could each convey distinct epigenetic information.  To investigate this, we engineered a variant of Drosophila melanogaster PRC2 which is converted into a mono-methyltransferase...
December 14, 2017: Genetics
Davide Michieletto, Michael Chiang, Davide Colì, Argyris Papantonis, Enzo Orlandini, Peter R Cook, Davide Marenduzzo
Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by 'writer' proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or 'readers', such as Polycomb Repressive Complexes and Transcription Factors...
January 9, 2018: Nucleic Acids Research
Vasanthi Dasari, Surabhi Srivastava, Shagufta Khan, Rakesh K Mishra
The process of aging is a hallmark of the natural life span of all organisms and individuals within a population show variability in the measures of age related performance. Longevity and the rate of aging are influenced by several factors such as genetics, nutrition, stress, and environment. Many studies have focused on the genes that impact aging and there is increasing evidence that epigenetic factors regulate these genes to control life span. Polycomb (PcG) and trithorax (trxG) protein complexes maintain the expression profiles of developmentally important genes and regulate many cellular processes...
February 2018: Biogerontology
Aneliya Yoveva, Ritwick Sawarkar
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a widely used technique for genome-wide mapping of protein-DNA interactions and epigenetic marks in vivo. Recent studies have suggested an important role of heat shock protein 90 (Hsp90) at chromatin. This molecular chaperone assists other proteins to acquire their mature and functional conformation and helps in the assembly of many complexes. In this chapter, we provide specific details on how to perform Hsp90 ChIP-seq from Drosophila Schneider (S2) cells...
2018: Methods in Molecular Biology
Pengfei Dong, Xiaoyu Tu, Po-Yu Chu, Peitao Lü, Ning Zhu, Donald Grierson, Baijuan Du, Pinghua Li, Silin Zhong
The spatial organization of the genome plays an important role in the regulation of gene expression. However, the core structural features of animal genomes, such as topologically associated domains (TADs) and chromatin loops, are not prominent in the extremely compact Arabidopsis genome. In this study, we examine the chromatin architecture, as well as their DNA methylation, histone modifications, accessible chromatin, and gene expression, of maize, tomato, sorghum, foxtail millet, and rice with genome sizes ranging from 0...
December 4, 2017: Molecular Plant
Noèlia Fernàndez-Castillo, Gabriela Gan, Marjolein M J van Donkelaar, Mariliis Vaht, Heike Weber, Wolfgang Retz, Andreas Meyer-Lindenberg, Barbara Franke, Jaanus Harro, Andreas Reif, Stephen V Faraone, Bru Cormand
The RBFOX1 gene (or A2BP1) encodes a splicing factor important for neuronal development that has been related to autism spectrum disorder and other neurodevelopmental phenotypes. Evidence from complementary sources suggests that this gene contributes to aggressive behavior. Suggestive associations with RBFOX1 have been identified in genome-wide association studies (GWAS) of anger, conduct disorder, and aggressive behavior. Nominal association signals in RBFOX1 were also found in an epigenome-wide association study (EWAS) of aggressive behavior...
November 23, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Diego I Cattoni, Andrés M Cardozo Gizzi, Mariya Georgieva, Marco Di Stefano, Alessandro Valeri, Delphine Chamousset, Christophe Houbron, Stephanie Déjardin, Jean-Bernard Fiche, Inma González, Jia-Ming Chang, Thomas Sexton, Marc A Marti-Renom, Frédéric Bantignies, Giacomo Cavalli, Marcelo Nollmann
At the kilo- to megabase pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combine high-content super-resolution microscopies with state-of-the-art DNA-labeling methods to reveal the variability in the multiscale organization of the Drosophila genome. We find that association frequencies within TADs and between TAD borders are below ~10%, independently of TAD size, epigenetic state, or cell type...
November 24, 2017: Nature Communications
Taylor J R Penke, Daniel J McKay, Brian D Strahl, A Gregory Matera, Robert J Duronio
Histone post-translational modifications (PTMs) and differential incorporation of variant and canonical histones into chromatin are central modes of epigenetic regulation. Despite similar protein sequences, histone variants are enriched for different suites of PTMs compared to their canonical counterparts. For example, variant histone H3.3 occurs primarily in transcribed regions and is enriched for "active" histone PTMs like Lys9 acetylation (H3.3K9ac), whereas the canonical histone H3 is enriched for Lys9 methylation (H3K9me), which is found in transcriptionally silent heterochromatin...
November 13, 2017: Genetics
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