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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
Tayaba Ismail, Hyun-Kyung Lee, Chowon Kim, Taejoon Kwon, Tae Joo Park, Hyun-Shik Lee
The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators)...
June 19, 2018: Epigenetics & Chromatin
Guanfeng Xu, Jie Zhang, Hao Lyu, Qisheng Song, Qili Feng, Hui Xiang, Sichun Zheng
BACKGROUND: Accurate regulation of tissue- and stage-specific expression of genes is prerequisite for normal development in organisms. DNA methylation plays an important role in modulating gene expression in mammals and plants. However, there is no direct evidence showing how DNA methylation regulates gene transcription in insects. RESULTS: During the development of Bombyx mori wing, the expression level of DNA methyltransferase 1 (BmDnmt1) gradually declined and became stationary at pupal stage, resulting in a lower methylation rate of the intragenic promoter of the mid-pupal wing-specific gene BmCHSA-2b, an epidermal chitin synthase controlling mid-pupal wing development in B...
June 14, 2018: Epigenetics & Chromatin
Jan Postberg, Franziska Jönsson, Patrick Philipp Weil, Aneta Bulic, Stefan Andreas Juranek, Hans-Joachim Lipps
BACKGROUND: During sexual reproduction in the unicellular ciliate Stylonychia somatic macronuclei differentiate from germline micronuclei. Thereby, programmed sequence reduction takes place, leading to the elimination of > 95% of germline sequences, which priorly adopt heterochromatin structure via H3K27me3. Simultaneously, 27nt-ncRNAs become synthesized from parental transcripts and are bound by the Argonaute protein PIWI1. RESULTS: These 27nt-ncRNAs cover sequences destined to the developing macronucleus and are thought to protect them from degradation...
June 12, 2018: Epigenetics & Chromatin
Veronica Garcia-Carpizo, Sergio Ruiz-Llorente, Jacinto Sarmentero, Osvaldo Graña-Castro, David G Pisano, Maria J Barrero
BACKGROUND: The reported antitumor activity of the BET family bromodomain inhibitors has prompted the development of inhibitors against other bromodomains. However, the human genome encodes more than 60 different bromodomains and most of them remain unexplored. RESULTS: We report that the bromodomains of the histone acetyltransferases CREBBP/EP300 are critical to sustain the proliferation of human leukemia and lymphoma cell lines. EP300 is very abundant at super-enhancers in K562 and is coincident with sites of GATA1 and MYC occupancy...
June 8, 2018: Epigenetics & Chromatin
Tao Wang, Matthew V Holt, Nicolas L Young
BACKGROUND: The dynamics of histone post-translational modifications (PTMs) are sparsely described, especially in their true physiological context of proteoforms (single histone molecules harboring combinations of PTMs). METHODS: Here we time-resolve the response of cells to SUV4-20 methyltransferase inhibition and unbiasedly quantitate the dynamic response of histone H4 PTMs and proteoforms. RESULTS: Contrary to the prevailing dogma, cells exhibit an immediate-early response with changes to histone proteoforms...
June 7, 2018: Epigenetics & Chromatin
Keiichiro Joh, Fumikazu Matsuhisa, Shuji Kitajima, Kenichi Nishioka, Ken Higashimoto, Hitomi Yatsuki, Tomohiro Kono, Haruhiko Koseki, Hidenobu Soejima
BACKGROUND: Zrsr1 is a paternally expressed imprinted gene located in the first intron of Commd1, and the Zrsr1 promoter resides in a differentially methylated region (DMR) that is maternally methylated in the oocyte. However, a mechanism for the establishment of the methylation has remained obscure. Commd1 is transcribed in the opposite direction to Zrsr1 with predominant maternal expression, especially in the adult brain. RESULTS: We found Commed1 transcribed through the DMR in the growing oocyte...
June 6, 2018: Epigenetics & Chromatin
Marco La Fortezza, Giovanna Grigolon, Andrea Cosolo, Alexey Pindyurin, Laura Breimann, Helmut Blum, Bas van Steensel, Anne-Kathrin Classen
BACKGROUND: Tracking dynamic protein-chromatin interactions in vivo is key to unravel transcriptional and epigenetic transitions in development and disease. However, limited availability and heterogeneous tissue composition of in vivo source material impose challenges on many experimental approaches. RESULTS: Here we adapt cell-type-specific DamID-seq profiling for use in Drosophila imaginal discs and make FLP/FRT-based induction accessible to GAL driver-mediated targeting of specific cell lineages...
June 5, 2018: Epigenetics & Chromatin
Kosuke Okazaki, Hiroaki Kato, Tetsushi Iida, Kaori Shinmyozu, Jun-Ichi Nakayama, Yota Murakami, Takeshi Urano
BACKGROUND: Heat-shock molecular chaperone proteins (Hsps) promote the loading of small interfering RNA (siRNA) onto RNA interference (RNAi) effector complexes. While the RNAi process is coupled with heterochromatin assembly in several model organisms, it remains unclear whether the Hsps contribute to epigenetic gene regulation. In this study, we used the fission yeast Schizosaccharomyces pombe as a model organism and investigated the roles of Hsp90 and Mas5 (a nucleocytoplasmic type-I Hsp40 protein) in RNAi-dependent heterochromatin assembly...
June 4, 2018: Epigenetics & Chromatin
Roderick C Slieker, Caroline L Relton, Tom R Gaunt, P Eline Slagboom, Bastiaan T Heijmans
BACKGROUND: The well-established association of chronological age with changes in DNA methylation is primarily founded on the analysis of large sets of blood samples, while conclusions regarding tissue-specificity are typically based on small number of samples, tissues and CpGs. Here, we systematically investigate the tissue-specific character of age-related DNA methylation changes at the level of the CpG, functional genomic region and nearest gene in a large dataset. RESULTS: We assembled a compendium of public data, encompassing genome-wide DNA methylation data (Illumina 450k array) on 8092 samples from 16 different tissues, including 7 tissues with moderate to high sample numbers (Dataset size range 96-1202, Ntotal  = 2858)...
May 30, 2018: Epigenetics & Chromatin
Elisabeth F Heuston, Cheryl A Keller, Jens Lichtenberg, Belinda Giardine, Stacie M Anderson, Ross C Hardison, David M Bodine
BACKGROUND: Enhancers and promoters are cis-acting regulatory elements associated with lineage-specific gene expression. Previous studies showed that different categories of active regulatory elements are in regions of open chromatin, and each category is associated with a specific subset of post-translationally marked histones. These regulatory elements are systematically activated and repressed to promote commitment of hematopoietic stem cells along separate differentiation paths, including the closely related erythrocyte (ERY) and megakaryocyte (MK) lineages...
May 28, 2018: Epigenetics & Chromatin
Shalima S Nair, Phuc-Loi Luu, Wenjia Qu, Madhavi Maddugoda, Lily Huschtscha, Roger Reddel, Georgia Chenevix-Trench, Martina Toso, James G Kench, Lisa G Horvath, Vanessa M Hayes, Phillip D Stricker, Timothy P Hughes, Deborah L White, John E J Rasko, Justin J-L Wong, Susan J Clark
BACKGROUND: Comprehensive genome-wide DNA methylation profiling is critical to gain insights into epigenetic reprogramming during development and disease processes. Among the different genome-wide DNA methylation technologies, whole genome bisulphite sequencing (WGBS) is considered the gold standard for assaying genome-wide DNA methylation at single base resolution. However, the high sequencing cost to achieve the optimal depth of coverage limits its application in both basic and clinical research...
May 28, 2018: Epigenetics & Chromatin
Kyunghwan Kim, Yonghwan Shin, Jinman Kim, Tobias S Ulmer, Woojin An
BACKGROUND: MMP-9 plays a direct role in the activation of pro-osteoclastogenic genes by cleaving histone H3N-terminal tail (H3NT) and altering chromatin architecture. Although H3 acetylation at K18 has been shown to stimulate MMP-9 enzymatic activity toward H3NT, nothing is known about the influence of other H3NT modifications on this epigenetic reaction. RESULTS: We show that H3 monomethylation at lysine 27 (H3K27me1) is essential for MMP-9-dependent H3NT proteolysis during RANKL-induced osteoclast differentiation...
May 28, 2018: Epigenetics & Chromatin
Thadeous J Kacmarczyk, Mame P Fall, Xihui Zhang, Yuan Xin, Yushan Li, Alicia Alonso, Doron Betel
BACKGROUND: DNA methylation in CpG context is fundamental to the epigenetic regulation of gene expression in higher eukaryotes. Changes in methylation patterns are implicated in many diseases, cellular differentiation, imprinting, and other biological processes. Techniques that enrich for biologically relevant genomic regions with high CpG content are desired, since, depending on the size of an organism's methylome, the depth of sequencing required to cover all CpGs can be prohibitively expensive...
May 25, 2018: Epigenetics & Chromatin
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