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Epigenetics & Chromatin

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https://www.readbyqxmd.com/read/28331549/dynamics-of-5-methylcytosine-and-5-hydroxymethylcytosine-during-pronuclear-development-in-equine-zygotes-produced-by-icsi
#1
Sonia Heras, Katrien Smits, Catharina De Schauwer, Ann Van Soom
BACKGROUND: Global epigenetic reprogramming is considered to be essential during embryo development to establish totipotency. In the classic model first described in the mouse, the genome-wide DNA demethylation is asymmetric between the paternal and the maternal genome. The paternal genome undergoes ten-eleven translocation (TET)-mediated active DNA demethylation, which is completed before the end of the first cell cycle. Since TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine, the latter is postulated to be an intermediate stage toward DNA demethylation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28293301/histone-peptide-microarray-screen-of-chromo-and-tudor-domains-defines-new-histone-lysine-methylation-interactions
#2
Erin K Shanle, Stephen A Shinsky, Joseph B Bridgers, Narkhyun Bae, Cari Sagum, Krzysztof Krajewski, Scott B Rothbart, Mark T Bedford, Brian D Strahl
BACKGROUND: Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized "reader" domains. Despite efforts to elucidate reader domain-PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28293300/silencing-markers-are-retained-on-pericentric-heterochromatin-during-murine-primordial-germ-cell-development
#3
Aristea Magaraki, Godfried van der Heijden, Esther Sleddens-Linkels, Leonidas Magarakis, Wiggert A van Cappellen, Antoine H F M Peters, Joost Gribnau, Willy M Baarends, Maureen Eijpe
BACKGROUND: In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins like heterochromatin-binding protein 1 isoforms (HP1 isoforms). Maintenance of this specialized chromatin structure is of great importance for genome integrity and for the controlled repression of the repetitive elements within the pericentric DNA sequence. Here we have studied histone modifications at pericentric heterochromatin during primordial germ cell (PGC) development using different fixation conditions and fluorescent immunohistochemical and immunocytochemical protocols...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28293299/identification-of-epigenetic-signature-associated-with-alpha-thalassemia-mental-retardation-x-linked-syndrome
#4
Laila C Schenkel, Kristin D Kernohan, Arran McBride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic
BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DNA methylation, while mutations in the ATRX gene may lead to the downstream epigenetic and transcriptional effects. Elucidating the underlying epigenetic mechanisms altered in ATR-X will provide a better understanding about the pathobiology of this disease, as well as provide novel diagnostic biomarkers...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28265301/assessing-histone-demethylase-inhibitors-in-cells-lessons-learned
#5
Stephanie B Hatch, Clarence Yapp, Raquel C Montenegro, Pavel Savitsky, Vicki Gamble, Anthony Tumber, Gian Filippo Ruda, Vassilios Bavetsias, Oleg Fedorov, Butrus Atrash, Florence Raynaud, Rachel Lanigan, LeAnne Carmichael, Kathy Tomlin, Rosemary Burke, Susan M Westaway, Jack A Brown, Rab K Prinjha, Elisabeth D Martinez, Udo Oppermann, Christopher J Schofield, Chas Bountra, Akane Kawamura, Julian Blagg, Paul E Brennan, Olivia Rossanese, Susanne Müller
BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active 'probe' molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28250819/smyd5-regulates-h4k20me3-marked-heterochromatin-to-safeguard-es-cell-self-renewal-and-prevent-spurious-differentiation
#6
Benjamin L Kidder, Gangqing Hu, Kairong Cui, Keji Zhao
BACKGROUND: Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated histone 4 lysine 20 (H4K20me3) in pluripotency and development are largely unknown. RESULTS: Here, we show that the histone lysine methyltransferase SMYD5 mediates H4K20me3 at heterochromatin regions. Depletion of SMYD5 leads to compromised self-renewal, including dysregulated expression of OCT4 targets, and perturbed differentiation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28239420/prc2-is-required-for-extensive-reorganization-of-h3k27me3-during-epigenetic-reprogramming-in-mouse-fetal-germ-cells
#7
Lexie Prokopuk, Jessica M Stringer, Kirsten Hogg, Kirstin D Elgass, Patrick S Western
BACKGROUND: Defining how epigenetic information is established in the germline during fetal development is key to understanding how epigenetic information is inherited and impacts on evolution and human health and disease. RESULTS: Here, we show that Polycomb Repressive Complex 2 is transiently localized in the nucleus of mouse fetal germ cells, while DNA methylation is removed from the germline. This coincides with significant enrichment of trimethylated lysine 27 on histone 3 near the nuclear lamina that is dependent on activity of the essential PRC2 catalytic proteins, Enhancer of Zeste 1 and/or 2...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28228846/decoupling-the-downstream-effects-of-germline-nuclear-rnai-reveals-that-h3k9me3-is-dispensable-for-heritable-rnai-and-the-maintenance-of-endogenous-sirna-mediated-transcriptional-silencing-in-caenorhabditis-elegans
#8
Natallia Kalinava, Julie Zhouli Ni, Kimberly Peterman, Esteban Chen, Sam Guoping Gu
BACKGROUND: Germline nuclear RNAi in C. elegans is a transgenerational gene-silencing pathway that leads to H3K9 trimethylation (H3K9me3) and transcriptional silencing at the target genes. H3K9me3 induced by either exogenous double-stranded RNA (dsRNA) or endogenous siRNA (endo-siRNA) is highly specific to the target loci and transgenerationally heritable. Despite these features, the role of H3K9me3 in siRNA-mediated transcriptional silencing and inheritance of the silencing state at native target genes is unclear...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28228845/histone-and-dna-methylation-control-by-h3-serine-10-threonine-11-phosphorylation-in-the-mouse-zygote
#9
Jie Lan, Konstantin Lepikhov, Pascal Giehr, Joern Walter
BACKGROUND: In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of histone H3 variants and distinct patterns of DNA and histone modifications. The molecular mechanisms linking histone variant-specific modifications and DNA methylation reprogramming during the first cell cycle remain to be clarified. RESULTS: Here, we show that the degree and distribution of H3K9me2 and of DNA modifications (5mC/5hmC) are influenced by the phosphorylation status of H3S10 and H3T11...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28149327/in-utero-exposure-to-maternal-smoking-is-associated-with-dna-methylation-alterations-and-reduced-neuronal-content-in-the-developing-fetal-brain
#10
Zac Chatterton, Brigham J Hartley, Man-Ho Seok, Natalia Mendelev, Sean Chen, Maria Milekic, Gorazd Rosoklija, Aleksandar Stankov, Iskra Trencevsja-Ivanovska, Kristen Brennand, Yongchao Ge, Andrew J Dwork, Fatemeh Haghighi
BACKGROUND: Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of cortical gray matter in childhood, indicating that prenatal exposure to tobacco may impact cortical development and manifest as behavioral problems. Cellular development is mediated by changes in epigenetic modifications such as DNA methylation, which can be affected by exposure to tobacco...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28149326/genome-wide-methylation-data-mirror-ancestry-information
#11
Elior Rahmani, Liat Shenhav, Regev Schweiger, Paul Yousefi, Karen Huen, Brenda Eskenazi, Celeste Eng, Scott Huntsman, Donglei Hu, Joshua Galanter, Sam S Oh, Melanie Waldenberger, Konstantin Strauch, Harald Grallert, Thomas Meitinger, Christian Gieger, Nina Holland, Esteban G Burchard, Noah Zaitlen, Eran Halperin
BACKGROUND: Genetic data are known to harbor information about human demographics, and genotyping data are commonly used for capturing ancestry information by leveraging genome-wide differences between populations. In contrast, it is not clear to what extent population structure is captured by whole-genome DNA methylation data. RESULTS: We demonstrate, using three large-cohort 450K methylation array data sets, that ancestry information signal is mirrored in genome-wide DNA methylation data and that it can be further isolated more effectively by leveraging the correlation structure of CpGs with cis-located SNPs...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28115992/sex-specific-chromatin-landscapes-in-an-ultra-compact-chordate-genome
#12
Pavla Navratilova, Gemma Barbara Danks, Abby Long, Stephen Butcher, John Robert Manak, Eric M Thompson
BACKGROUND: In multicellular organisms, epigenome dynamics are associated with transitions in the cell cycle, development, germline specification, gametogenesis and inheritance. Evolutionarily, regulatory space has increased in complex metazoans to accommodate these functions. In tunicates, the sister lineage to vertebrates, we examine epigenome adaptations to strong secondary genome compaction, sex chromosome evolution and cell cycle modes. RESULTS: Across the 70 MB Oikopleura dioica genome, we profiled 19 histone modifications, and RNA polymerase II, CTCF and p300 occupancies, to define chromatin states within two homogeneous tissues with distinct cell cycle modes: ovarian endocycling nurse nuclei and mitotically proliferating germ nuclei in testes...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28096900/ms_histonedb-a-manually-curated-resource-for-proteomic-analysis-of-human-and-mouse-histones
#13
Sara El Kennani, Annie Adrait, Alexey K Shaytan, Saadi Khochbin, Christophe Bruley, Anna R Panchenko, David Landsman, Delphine Pflieger, Jérôme Govin
BACKGROUND: Histones and histone variants are essential components of the nuclear chromatin. While mass spectrometry has opened a large window to their characterization and functional studies, their identification from proteomic data remains challenging. Indeed, the current interpretation of mass spectrometry data relies on public databases which are either not exhaustive (Swiss-Prot) or contain many redundant entries (UniProtKB or NCBI). Currently, no protein database is ideally suited for the analysis of histones and the complex array of mammalian histone variants...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28035242/the-detailed-3d-multi-loop-aggregate-rosette-chromatin-architecture-and-functional-dynamic-organization-of-the-human-and-mouse-genomes
#14
Tobias A Knoch, Malte Wachsmuth, Nick Kepper, Michael Lesnussa, Anis Abuseiris, A M Ali Imam, Petros Kolovos, Jessica Zuin, Christel E M Kockx, Rutger W W Brouwer, Harmen J G van de Werken, Wilfred F J van IJcken, Kerstin S Wendt, Frank G Grosveld
BACKGROUND: The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function-the storage, expression, and replication of genetic information-is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture (T2C), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28035241/dynamic-properties-of-independent-chromatin-domains-measured-by-correlation-spectroscopy-in-living-cells
#15
Malte Wachsmuth, Tobias A Knoch, Karsten Rippe
BACKGROUND: Genome organization into subchromosomal topologically associating domains (TADs) is linked to cell-type-specific gene expression programs. However, dynamic properties of such domains remain elusive, and it is unclear how domain plasticity modulates genomic accessibility for soluble factors. RESULTS: Here, we combine and compare a high-resolution topology analysis of interacting chromatin loci with fluorescence correlation spectroscopy measurements of domain dynamics in single living cells...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27980682/-gap-hunting-to-characterize-clustered-probe-signals-in-illumina-methylation-array-data
#16
Shan V Andrews, Christine Ladd-Acosta, Andrew P Feinberg, Kasper D Hansen, M Daniele Fallin
BACKGROUND: The Illumina 450k array has been widely used in epigenetic association studies. Current quality-control (QC) pipelines typically remove certain sets of probes, such as those containing a SNP or with multiple mapping locations. An additional set of potentially problematic probes are those with DNA methylation distributions characterized by two or more distinct clusters separated by gaps. Data-driven identification of such probes may offer additional insights for downstream analyses...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27980681/targeted-bisulfite-sequencing-of-the-dynamic-dna-methylome
#17
Michael J Ziller, Elena K Stamenova, Hongcang Gu, Andreas Gnirke, Alexander Meissner
BACKGROUND: The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of theoretically capturing all cytosines in the genome at single-nucleotide resolution, but it has a number of significant practical drawbacks that become amplified with increasing sample numbers. All other technologies capture only a fraction of the cytosines that show dynamic regulation across cell and tissue types...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27980680/hoxa-repression-is-mediated-by-nucleoporin-nup93-assisted-by-its-interactors-nup188-and-nup205
#18
Ajay S Labade, Krishanpal Karmodiya, Kundan Sengupta
BACKGROUND: The nuclear pore complex (NPC) mediates nuclear transport of RNA and proteins into and out of the nucleus. Certain nucleoporins have additional functions in chromatin organization and transcription regulation. Nup93 is a scaffold nucleoporin at the nuclear pore complex which is associated with human chromosomes 5, 7 and 16 and with the promoters of the HOXA gene as revealed by ChIP-on-chip studies using tiling microarrays for these chromosomes. However, the functional consequences of the association of Nup93 with HOXA is unknown...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27895716/widespread-recovery-of-methylation-at-gametic-imprints-in-hypomethylated-mouse-stem-cells-following-rescue-with-dnmt3a2
#19
Avinash Thakur, Sarah-Jayne Mackin, Rachelle E Irwin, Karla M O'Neill, Gareth Pollin, Colum Walsh
BACKGROUND: Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27895715/protein-kinase-msk1-physically-and-functionally-interacts-with-the-kmt2a-mll1-methyltransferase-complex-and-contributes-to-the-regulation-of-multiple-target-genes
#20
Maaike Wiersma, Marianne Bussiere, John A Halsall, Nil Turan, Robert Slany, Bryan M Turner, Karl P Nightingale
BACKGROUND: The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear...
2016: Epigenetics & Chromatin
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