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Epigenetics & Chromatin

Fatemeh Behjati Ardakani, Kathrin Kattler, Karl Nordström, Nina Gasparoni, Gilles Gasparoni, Sarah Fuchs, Anupam Sinha, Matthias Barann, Peter Ebert, Jonas Fischer, Barbara Hutter, Gideon Zipprich, Charles D Imbusch, Bärbel Felder, Jürgen Eils, Benedikt Brors, Thomas Lengauer, Thomas Manke, Philip Rosenstiel, Jörn Walter, Marcel H Schulz
BACKGROUND: Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs...
November 10, 2018: Epigenetics & Chromatin
Alexey V Pindyurin, Artem A Ilyin, Anton V Ivankin, Mikhail V Tselebrovsky, Valentina V Nenasheva, Elena A Mikhaleva, Ludo Pagie, Bas van Steensel, Yuri Y Shevelyov
BACKGROUND: In most mammalian cell lines, chromatin located at the nuclear periphery is represented by condensed heterochromatin, as evidenced by microscopy observations and DamID mapping of lamina-associated domains (LADs) enriched in dimethylated Lys9 of histone H3 (H3K9me2). However, in Kc167 cell culture, the only Drosophilla cell type where LADs have previously been mapped, they are neither H3K9me2-enriched nor overlapped with the domains of heterochromatin protein 1a (HP1a). RESULTS: Here, using cell type-specific DamID we mapped genome-wide LADs, HP1a and Polycomb (Pc) domains from the central brain, Repo-positive glia, Elav-positive neurons and the fat body of Drosophila third instar larvae...
November 1, 2018: Epigenetics & Chromatin
Aaron J Storey, Hsin-Ping Wang, Reine U Protacio, Mari K Davidson, Alan J Tackett, Wayne P Wahls
BACKGROUND: Meiotic recombination hotspots control the frequency and distribution of Spo11 (Rec12)-initiated recombination in the genome. Recombination occurs within and is regulated in part by chromatin structure, but relatively few of the many chromatin remodeling factors and histone posttranslational modifications (PTMs) have been interrogated for a role in the process. RESULTS: We developed a chromatin affinity purification and mass spectrometry-based approach to identify proteins and histone PTMs that regulate recombination hotspots...
October 29, 2018: Epigenetics & Chromatin
Chaini Konwar, E Magda Price, Li Qing Wang, Samantha L Wilson, Jefferson Terry, Wendy P Robinson
BACKGROUND: Placental inflammation, often presenting as acute chorioamnionitis (aCA), is commonly associated with preterm birth. Preterm birth can have both immediate and long-term adverse effects on the health of the baby. Developing biomarkers of inflammation in the placenta can help to understand its effects and potentially lead to new approaches for rapid prenatal diagnosis of aCA. We aimed to characterize epigenetic variation associated with aCA in placenta (chorionic villi) and fetal membranes (chorion and amnion) to better understand how aCA may impact processes that lead to preterm birth...
October 29, 2018: Epigenetics & Chromatin
Hangnoh Lee, Brian Oliver
BACKGROUND: In animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in male Drosophila, there is a dosage compensation complex (MSL) that equilibrates X-linked gene expression with the autosomes. There are other potential contributions to dosage compensation. Hemizygous autosomal genes located in repressive chromatin domains are often derepressed. If this homolog-dependent repression occurs on the X, which has no pairing partner, then derepression could contribute to male dosage compensation...
October 24, 2018: Epigenetics & Chromatin
Francesco Natale, Annina Scholl, Alexander Rapp, Wei Yu, Cathia Rausch, M Cristina Cardoso
BACKGROUND: Preservation of genome integrity by complete, error-free DNA duplication prior to cell division and by correct DNA damage repair is paramount for the development and maintenance of an organism. This holds true not only for protein-encoding genes, but also it applies to repetitive DNA elements, which make up more than half of the human genome. Here, we focused on the replication and repair kinetics of interspersed and tandem repetitive DNA elements. RESULTS: We integrated genomic population level data with a single cell immunofluorescence in situ hybridization approach to simultaneously label replication/repair and repetitive DNA elements...
October 23, 2018: Epigenetics & Chromatin
Sarah Wyck, Carolina Herrera, Cristina E Requena, Lilli Bittner, Petra Hajkova, Heinrich Bollwein, Raffaella Santoro
BACKGROUND: Reactive oxygen species (ROS)-induced oxidative stress is well known to play a major role in male infertility. Sperm are sensitive to ROS damaging effects because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. However, how oxidative DNA lesions in sperm affect early embryonic development remains elusive. RESULTS: Using cattle as model, we show that fertilization using sperm exposed to oxidative stress caused a major developmental arrest at the time of embryonic genome activation...
October 17, 2018: Epigenetics & Chromatin
Louie N van de Lagemaat, Maria Flenley, Magnus D Lynch, David Garrick, Simon R Tomlinson, Kamil R Kranc, Douglas Vernimmen
BACKGROUND: The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. This is particularly important at regulatory regions, such as CpG islands (CGIs), which are known to recruit Trithorax (TrxG) and Polycomb group proteins. The CxxC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit of the TrxG SET1 protein complex, a major catalyst of trimethylation of H3K4 (H3K4me3). RESULTS: Here, we used ChIP followed by high-throughput sequencing (ChIP-seq) to analyse genomic occupancy of CFP1 in two human haematopoietic cell types...
October 6, 2018: Epigenetics & Chromatin
Xinwei Wu, Gang Li, Ruiyu Xie
Since the discovery of methylcytosine oxidase ten-eleven translocation (TET) proteins, we have witnessed an exponential increase in studies examining their roles in epigenetic regulation. TET family proteins catalyze the sequential oxidation of 5-methylcytosine (5mC) to oxidized methylcytosines including 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. TETs contribute to the regulation of lineage-specific gene expression via modulating DNA 5mC/5hmC balances at the proximal and distal regulatory elements of cell identity genes, and therefore enhance chromatin accessibility and gene transcription...
October 5, 2018: Epigenetics & Chromatin
Fanny Gatzmann, Cassandra Falckenhayn, Julian Gutekunst, Katharina Hanna, Günter Raddatz, Vitor Coutinho Carneiro, Frank Lyko
BACKGROUND: The parthenogenetic marbled crayfish (Procambarus virginalis) is a novel species that has rapidly invaded and colonized various different habitats. Adaptation to different environments appears to be independent of the selection of genetic variants, but epigenetic programming of the marbled crayfish genome remains to be understood. RESULTS: Here, we provide a comprehensive analysis of DNA methylation in marbled crayfish. Whole-genome bisulfite sequencing of multiple replicates and different tissues revealed a methylation pattern that is characterized by gene body methylation of housekeeping genes...
October 4, 2018: Epigenetics & Chromatin
Takeshi Tsusaka, Masaki Kikuchi, Tadahiro Shimazu, Takehiro Suzuki, Yoshihiro Sohtome, Mai Akakabe, Mikiko Sodeoka, Naoshi Dohmae, Takashi Umehara, Yoichi Shinkai
BACKGROUND: G9a and the related enzyme GLP were originally identified as histone lysine methyltransferases and then shown to also methylate several other non-histone proteins. RESULTS: Here, we performed a comprehensive screen to identify their substrates in mouse embryonic stem cells (mESCs). We identified 59 proteins, including histones and other known substrates. One of the identified substrates, activating transcriptional factor 7-interacting protein 1 (ATF7IP), is tri-methylated at a histone H3 lysine 9 (H3K9)-like mimic by the G9a/GLP complex, although this complex mainly introduces di-methylation on H3K9 and DNA ligase 1 (LIG1) K126 in cells...
October 4, 2018: Epigenetics & Chromatin
Shunsuke Suzuki, Geoffrey Shaw, Marilyn B Renfree
BACKGROUND: Genomic imprinting leads to maternal expression of IGF2R in both mouse and opossum. In mouse, the antisense long noncoding (lnc) RNA Airn, which is paternally expressed from the differentially methylated region (DMR) in the second intron of Igf2r, is required to silence the paternal Igf2r. In opossum, however, intriguingly, the DMR was reported to be in a different downstream intron (intron 11) and there was no antisense lncRNA detected in previous analyses. Therefore, clarifying the imprinting mechanism of marsupial IGF2R is of great relevance for understanding the origin and evolution of genomic imprinting in the IGF2R locus...
September 29, 2018: Epigenetics & Chromatin
Jenny van Dongen, Erik A Ehli, Rick Jansen, Catharina E M van Beijsterveldt, Gonneke Willemsen, Jouke J Hottenga, Noah A Kallsen, Shanna A Peyton, Charles E Breeze, Cornelis Kluft, Bastiaan T Heijmans, Meike Bartels, Gareth E Davies, Dorret I Boomsma
BACKGROUND: DNA methylation arrays are widely used in epigenome-wide association studies and methylation quantitative trait locus (mQTL) studies. Here, we performed the first genome-wide analysis of monozygotic (MZ) twin correlations and mQTLs on data obtained with the Illumina MethylationEPIC BeadChip (EPIC array) and compared the performance of the EPIC array to the Illumina HumanMethylation450 BeadChip (HM450 array) for buccal-derived DNA. RESULTS: Good-quality EPIC data were obtained for 102 buccal-derived DNA samples from 49 MZ twin pairs (mean age = 7...
September 25, 2018: Epigenetics & Chromatin
Taro Tsujimura, Osamu Takase, Masahiro Yoshikawa, Etsuko Sano, Matsuhiko Hayashi, Tsuyoshi Takato, Atsushi Toyoda, Hideyuki Okano, Keiichi Hishikawa
BACKGROUND: Contact domains of chromatin serve as a fundamental unit to regulate action of enhancers for target genes. Looping between a pair of CCCTC-binding factor (CTCF)-binding sites in convergent orientations underlies the formation of contact domains, while those in divergent orientations establish domain boundaries. However, every CTCF site is not necessarily engaged in loop or boundary structures, leaving functions of CTCF in varied genomic contexts still elusive. The locus containing Tfap2c and Bmp7 encompasses two contact domains separated by a region between the two genes, termed transition zone (TZ), characterized by two arrays of CTCF sites in divergent configuration...
September 14, 2018: Epigenetics & Chromatin
Leonor Rib, Dominic Villeneuve, Shilpi Minocha, Viviane Praz, Nouria Hernandez, Nicolas Guex, Winship Herr
BACKGROUND: Compensatory liver hyperplasia-or regeneration-induced by two-thirds partial hepatectomy (PH) permits the study of synchronized activation of mammalian gene expression, particularly in relation to cell proliferation. Here, we measured genomic transcriptional responses and mRNA accumulation changes after PH and sham surgeries. RESULTS: During the first 10-20 h, the PH- and sham-surgery responses were very similar, including parallel early activation of cell-division-cycle genes...
September 12, 2018: Epigenetics & Chromatin
Xin Sun, Justin C St John
BACKGROUND: There are multiple copies of mitochondrial DNA (mtDNA) present in each cell type, and they are strictly regulated in a cell-specific manner by a group of nuclear-encoded mtDNA-specific replication factors. This strict regulation of mtDNA copy number is mediated by cell-specific DNA methylation of these replication factors. Glioblastoma multiforme, HSR-GBM1, cells are hyper-methylated and maintain low mtDNA copy number to support their tumorigenic status. We have previously shown that when HSR-GBM1 cells with 50% of their original mtDNA content were inoculated into mice, tumours grew more aggressively than non-depleted cells...
September 12, 2018: Epigenetics & Chromatin
Robin L Adrianse, Kaleb Smith, Tonibelle Gatbonton-Schwager, Smitha P Sripathy, Uyen Lao, Eric J Foss, Ruben G Boers, Joachim B Boers, Joost Gribnau, Antonio Bedalov
BACKGROUND: The long noncoding RNA Xist is critical for initiation and establishment of X-chromosome inactivation during embryogenesis in mammals, but it is unclear whether its continued expression is required for maintaining X-inactivation in vivo. RESULTS: By using an inactive X-chromosome-linked MeCP2-GFP reporter, which allowed us to enumerate reactivation events in the mouse brain even when they occur in very few cells, we found that deletion of Xist in the brain after establishment of X-chromosome inactivation leads to reactivation in 2-5% of neurons and in a smaller fraction of astrocytes...
August 31, 2018: Epigenetics & Chromatin
Idan Nurick, Ron Shamir, Ran Elkon
BACKGROUND: Our appreciation of the critical role of the genome's 3D organization in gene regulation is steadily increasing. Recent 3C-based deep sequencing techniques elucidated a hierarchy of structures that underlie the spatial organization of the genome in the nucleus. At the top of this hierarchical organization are chromosomal territories and the megabase-scale A/B compartments that correlate with transcriptional activity within cells. Below them are the relatively cell-type-invariant topologically associated domains (TADs), characterized by high frequency of physical contacts between loci within the same TAD, and are assumed to function as regulatory units...
August 29, 2018: Epigenetics & Chromatin
Dong Cheng, Tingcai Cheng, Xi Yang, Quan Zhang, Jianfeng Fu, Tieshan Feng, Jiao Gong, Qingyou Xia
BACKGROUND: The silkworm, Bombyx mori, a typical representative of metamorphic insects, is of great agricultural and economic importance. The steroid hormone ecdysone (20-hydroxyecdysone, 20E) is the central regulator of insect developmental transitions, and its nuclear receptors are crucial for numerous biological processes, including reproduction, metabolism, and immunity. However, genome-wide DNA regulatory elements and the ecdysone receptor (EcR) that control these programs of gene expression are not well defined...
August 27, 2018: Epigenetics & Chromatin
Premi Haynes, Karol Bomsztyk, Daniel G Miller
BACKGROUND: Facioscapulohumeral muscular dystrophy 1 (FSHD1) has an autosomal dominant pattern of inheritance and primarily affects skeletal muscle. The genetic cause of FSHD1 is contraction of the D4Z4 macrosatellite array on chromosome 4 alleles associated with a permissive haplotype causing infrequent sporadic expression of the DUX4 gene. Epigenetically, the contracted D4Z4 array has decreased cytosine methylation and an open chromatin structure. Despite these genetic and epigenetic changes, the majority of FSHD myoblasts are able to repress DUX4 transcription...
August 20, 2018: Epigenetics & Chromatin
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