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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
Abhinav Adhikari, Judith Davie
BACKGROUND: JARID2 is a non-catalytic member of the polycomb repressive complex 2 (PRC2), which is known to regulate developmental target genes in embryonic stem cells. Here, we provide mechanistic insight into the modulation of Wnt signaling by JARID2 during murine skeletal muscle differentiation. RESULTS: We show that JARID2 is expressed in proliferating myoblasts, but downregulated upon muscle differentiation. Unexpectedly, depletion of JARID2 or the catalytic subunit of the PRC2 complex, EZH2, inhibited differentiation, suggesting that JARID2 and the PRC2 complex are required to initiate this process...
August 17, 2018: Epigenetics & Chromatin
Zhuo Sun, Brian P Chadwick
BACKGROUND: The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a candidate for maintaining this repressive modification at the human Xi. RESULTS: Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes at the Xi, but unexpectedly we observed striking decompaction of the Xi territory...
August 13, 2018: Epigenetics & Chromatin
Peng A, Xinyi Xu, Chenglin Wang, Jing Yang, Shida Wang, Jiewen Dai, Ling Ye
BACKGROUND: Proliferating cell nuclear antigen (PCNA), a ring-shaped homotrimer complex, promotes DNA replication via binding to DNA polymerase. Trimerized PCNA is critical for DNA replication. Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. However, how EZH2 promotes proliferation by controlling DNA replication through PCNA remains elusive. RESULTS: Here, we showed that low EZH2 levels repressed the proliferation of human dental pulp cells (hDPCs)...
August 2, 2018: Epigenetics & Chromatin
Philip A Ruzycki, Xiaodong Zhang, Shiming Chen
BACKGROUND: Recent technological advances have delivered the genome-wide targets of many important transcription factors (TFs). However, increasing evidence suggests that not all target sites mediate regulatory function, raising the questions of how to determine which sites are active, what are the epigenetic consequences of TF binding at these sites, and how the specificity is coded. To address these questions, we focused on CRX, a disease-associated homeodomain TF required for photoreceptor gene expression and development...
August 1, 2018: Epigenetics & Chromatin
Laxmi Narayan Mishra, Vasantha Shalini, Nikhil Gupta, Krittika Ghosh, Neeraj Suthar, Utsa Bhaduri, M R Satyanarayana Rao
BACKGROUND: Linker histones establish and maintain higher-order chromatin structure. Eleven linker histone subtypes have been reported in mammals. HILS1 is a spermatid-specific linker histone, and its expression overlaps with the histone-protamine exchange process during mammalian spermiogenesis. However, the role of HILS1 in spermatid chromatin remodeling is largely unknown. RESULTS: In this study, we demonstrate using circular dichroism spectroscopy that HILS1 is a poor condenser of DNA and chromatin compared to somatic linker histone H1d...
August 1, 2018: Epigenetics & Chromatin
Gilles Gasparoni, Sebastian Bultmann, Pavlo Lutsik, Theo F J Kraus, Sabrina Sordon, Julia Vlcek, Vanessa Dietinger, Martina Steinmaurer, Melanie Haider, Christopher B Mulholland, Thomas Arzberger, Sigrun Roeber, Matthias Riemenschneider, Hans A Kretzschmar, Armin Giese, Heinrich Leonhardt, Jörn Walter
BACKGROUND: Epigenome-wide association studies (EWAS) based on human brain samples allow a deep and direct understanding of epigenetic dysregulation in Alzheimer's disease (AD). However, strong variation of cell-type proportions across brain tissue samples represents a significant source of data noise. Here, we report the first EWAS based on sorted neuronal and non-neuronal (mostly glia) nuclei from postmortem human brain tissues. RESULTS: We show that cell sorting strongly enhances the robust detection of disease-related DNA methylation changes even in a relatively small cohort...
July 25, 2018: Epigenetics & Chromatin
Elizaveta Radion, Valeriya Morgunova, Sergei Ryazansky, Natalia Akulenko, Sergey Lavrov, Yuri Abramov, Pavel A Komarov, Sergey I Glukhov, Ivan Olovnikov, Alla Kalmykova
BACKGROUND: Telomeric small RNAs related to PIWI-interacting RNAs (piRNAs) have been described in various eukaryotes; however, their role in germline-specific telomere function remains poorly understood. Using a Drosophila model, we performed an in-depth study of the biogenesis of telomeric piRNAs and their function in telomere homeostasis in the germline. RESULTS: To fully characterize telomeric piRNA clusters, we integrated the data obtained from analysis of endogenous telomeric repeats, as well as transgenes inserted into different telomeric and subtelomeric regions...
July 12, 2018: Epigenetics & Chromatin
Simone Roeh, Tobias Wiechmann, Susann Sauer, Maik Ködel, Elisabeth B Binder, Nadine Provençal
BACKGROUND: The ability to accurately and efficiently measure DNA methylation is critical to advance the understanding of this epigenetic mechanism and its contribution to common diseases. Here, we present a highly accurate method to measure methylation using bisulfite sequencing (termed HAM-TBS). This novel method is able to assess DNA methylation in multiple samples with high accuracy in a cost-effective manner. We developed this assay for the FKBP5 locus, an important gene in the regulation of the stress system and previously linked to stress-related disorders, but the method is applicable to any locus of interest...
July 4, 2018: Epigenetics & Chromatin
Marco La Fortezza, Giovanna Grigolon, Andrea Cosolo, Alexey Pindyurin, Laura Breimann, Helmut Blum, Bas van Steensel, Anne-Kathrin Classen
Unfortunately, the original version of this article contained a typographical error in one of the author names. The name of the author Alexey Pindyurin was incorrectly spelt as Alexey Pinduyrin. The correct spelling is included here and has been updated in the original article.
July 3, 2018: Epigenetics & Chromatin
Hitomi Matsuzaki, Eiichi Okamura, Daichi Kuramochi, Aki Ushiki, Katsuhiko Hirakawa, Akiyoshi Fukamizu, Keiji Tanimoto
BACKGROUND: Genomic imprinting is governed by allele-specific DNA methylation at imprinting control regions (ICRs), and the mechanism controlling its differential methylation establishment during gametogenesis has been a subject of intensive research interest. However, recent studies have reported that gamete methylation is not restricted at the ICRs, thus highlighting the significance of ICR methylation maintenance during the preimplantation period where genome-wide epigenetic reprogramming takes place...
June 29, 2018: Epigenetics & Chromatin
Dafni Anastasiadi, Anna Esteve-Codina, Francesc Piferrer
BACKGROUND: DNA methylation is one of the main epigenetic mechanisms for the regulation of gene expression in eukaryotes. In the standard model, methylation in gene promoters has received the most attention since it is generally associated with transcriptional silencing. Nevertheless, recent studies in human tissues reveal that methylation of the region downstream of the transcription start site is highly informative of gene expression. Also, in some cell types and specific genes it has been found that methylation of the first intron, a gene feature typically rich in enhancers, is linked with gene expression...
June 29, 2018: Epigenetics & Chromatin
Bettina M Fuglerud, Marit Ledsaak, Marie Rogne, Ragnhild Eskeland, Odd S Gabrielsen
BACKGROUND: The concept of pioneer transcription factors is emerging as an essential part of the epigenetic regulation, taking place during cell development and differentiation. However, the precise molecular mechanism underlying pioneer factor activity remains poorly understood. We recently reported that the transcription factor c-Myb acts as a pioneer factor in haematopoiesis, and a point mutation in its DNA binding domain, D152V, is able to abrogate this function. RESULTS: Here, we show that specific histone modifications, including H3K27ac, prevent binding of c-Myb to histone tails, representing a novel effect of histone modifications, namely restricting binding of a pioneer factor to chromatin...
June 28, 2018: Epigenetics & Chromatin
Kai O Hensel, Franziska Cantner, Felix Bangert, Stefan Wirth, Jan Postberg
BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of cccDNA and HBx remains unexplored. RESULTS: To identify virus-host genome interactions and the underlying nuclear landscape for the first time, we combined circular chromosome conformation capture (4C) with RNA-seq and ChIP-seq...
June 22, 2018: Epigenetics & Chromatin
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