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Epigenetics & Chromatin

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https://www.readbyqxmd.com/read/28533820/medip-seq-and-ncpg-analyses-illuminate-sexually-dimorphic-methylation-of-gonadal-development-genes-with-high-historic-methylation-in-turtle-hatchlings-with-temperature-dependent-sex-determination
#1
Srihari Radhakrishnan, Robert Literman, Beatriz Mizoguchi, Nicole Valenzuela
BACKGROUND: DNA methylation alters gene expression but not DNA sequence and mediates some cases of phenotypic plasticity. Temperature-dependent sex determination (TSD) epitomizes phenotypic plasticity where environmental temperature drives embryonic sexual fate, as occurs commonly in turtles. Importantly, the temperature-specific transcription of two genes underlying gonadal differentiation is known to be induced by differential methylation in TSD fish, turtle and alligator. Yet, how extensive is the link between DNA methylation and TSD remains unclear...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28515788/genomic-imprinting-does-not-reduce-the-dosage-of-ube3a-in-neurons
#2
Paul R Hillman, Sarah G B Christian, Ryan Doan, Noah D Cohen, Kranti Konganti, Kory Douglas, Xu Wang, Paul B Samollow, Scott V Dindot
BACKGROUND: The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types. Both loss-of-function and gain-of-function mutations affecting the dosage of UBE3A are associated with several neurodevelopmental syndromes and psychological conditions, suggesting that UBE3A is dosage-sensitive in the brain. The observation that loss of imprinting increases the dosage of UBE3A in brain further suggests that inactivation of the paternal UBE3A allele evolved as a dosage-regulating mechanism...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28515787/a-computational-approach-for-the-functional-classification-of-the-epigenome
#3
Francesco Gandolfi, Anna Tramontano
BACKGROUND: In the last decade, advanced functional genomics approaches and deep sequencing have allowed large-scale mapping of histone modifications and other epigenetic marks, highlighting functional relationships between chromatin organization and genome function. Here, we propose a novel approach to explore functional interactions between different epigenetic modifications and extract combinatorial profiles that can be used to annotate the chromatin in a finite number of functional classes...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28507606/transcription-and-chromatin-determinants-of-de-novo-dna-methylation-timing-in-oocytes
#4
Lenka Gahurova, Shin-Ichi Tomizawa, Sébastien A Smallwood, Kathleen R Stewart-Morgan, Heba Saadeh, Jeesun Kim, Simon R Andrews, Taiping Chen, Gavin Kelsey
BACKGROUND: Gametogenesis in mammals entails profound re-patterning of the epigenome. In the female germline, DNA methylation is acquired late in oogenesis from an essentially unmethylated baseline and is established largely as a consequence of transcription events. Molecular and functional studies have shown that imprinted genes become methylated at different times during oocyte growth; however, little is known about the kinetics of methylation gain genome wide and the reasons for asynchrony in methylation at imprinted loci...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28503202/stabilization-of-foxp3-expression-by-crispr-dcas9-based-epigenome-editing-in-mouse-primary-t-cells
#5
Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura
BACKGROUND: Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. RESULTS: In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28503201/dna-methylation-and-dna-methyltransferases
#6
REVIEW
John R Edwards, Olya Yarychkivska, Mathieu Boulard, Timothy H Bestor
The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perceived, when the number of protein-encoding mammalian genes was believed to be at least five times greater than the actual number, and when it was not understood that only ~10% of the genome is under selective pressure and likely to have biological function. We use more recent findings from genome biology and whole-genome methylation profiling to provide a reappraisal of the shape of genomic methylation patterns and the nature of the changes that they undergo during gametogenesis and early development...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28465725/differential-dna-methylation-and-lymphocyte-proportions-in-a-costa-rican-high-longevity-region
#7
Lisa M McEwen, Alexander M Morin, Rachel D Edgar, Julia L MacIsaac, Meaghan J Jones, William H Dow, Luis Rosero-Bixby, Michael S Kobor, David H Rehkopf
BACKGROUND: The Nicoya Peninsula in Costa Rica has one of the highest old-age life expectancies in the world, but the underlying biological mechanisms of this longevity are not well understood. As DNA methylation is hypothesized to be a component of biological aging, we focused on this malleable epigenetic mark to determine its association with current residence in Nicoya versus elsewhere in Costa Rica. Examining a population's unique DNA methylation pattern allows us to differentiate hallmarks of longevity from individual stochastic variation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28428825/comprehensive-evaluation-of-genome-wide-5-hydroxymethylcytosine-profiling-approaches-in-human-dna
#8
Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M Gould, Shalima S Nair, Susan J Clark, Clare Stirzaker
BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28413451/differential-dna-methylation-at-conserved-non-genic-elements-and-evidence-for-transgenerational-inheritance-following-developmental-exposure-to-mono-2-ethylhexyl-phthalate-and-5-azacytidine-in-zebrafish
#9
Jorke H Kamstra, Liana Bastos Sales, Peter Aleström, Juliette Legler
BACKGROUND: Exposure to environmental stressors during development may lead to latent and transgenerational adverse health effects. To understand the role of DNA methylation in these effects, we used zebrafish as a vertebrate model to investigate heritable changes in DNA methylation following chemical-induced stress during early development. We exposed zebrafish embryos to non-embryotoxic concentrations of the biologically active phthalate metabolite mono(2-ethylhexyl) phthalate (MEHP, 30 µM) and the DNA methyltransferase 1 inhibitor 5-azacytidine (5AC, 10 µM)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28413450/fetal-testis-organ-culture-reproduces-the-dynamics-of-epigenetic-reprogramming-in-rat-gonocytes
#10
Arlette Rwigemera, Fabien Joao, Geraldine Delbes
BACKGROUND: Epigenetic reprogramming is a critical step in male germ cell development that occurs during perinatal life. It is characterized by the remodeling of different epigenetic marks such as DNA methylation (5mC) and methylation of histone H3. It has been suggested that endocrine disruptors can affect the male germline epigenome by altering epigenetic reprogramming, but the mechanisms involved are still unknown. We have previously used an organ culture system that maintains the development of the different fetal testis cell types, to evaluate the effects of various endocrine disruptors on gametogenesis and steroidogenesis in the rat...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28413449/links-between-dna-methylation-and-nucleosome-occupancy-in-the-human-genome
#11
Clayton K Collings, John N Anderson
BACKGROUND: DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28396698/internal-modifications-in-the-cenp-a-nucleosome-modulate-centromeric-dynamics
#12
Minh Bui, Mary Pitman, Arthur Nuccio, Serene Roque, Paul Gregory Donlin-Asp, Aleksandra Nita-Lazar, Garegin A Papoian, Yamini Dalal
BACKGROUND: Posttranslational modifications of core histones are correlated with changes in transcriptional status, chromatin fiber folding, and nucleosome dynamics. However, within the centromere-specific histone H3 variant CENP-A, few modifications have been reported, and their functions remain largely unexplored. In this multidisciplinary report, we utilize in silico computational and in vivo approaches to dissect lysine 124 of human CENP-A, which was previously reported to be acetylated in advance of replication...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28344658/flightless-i-governs-cell-fate-by-recruiting-the-sumo-isopeptidase-senp3-to-distinct-hox-genes
#13
Arnab Nayak, Anja Reck, Christian Morsczeck, Stefan Müller
BACKGROUND: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. RESULTS: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28344657/well-positioned-nucleosomes-punctuate-polycistronic-pol-ii-transcription-units-and-flank-silent-vsg-gene-arrays-in-trypanosoma-brucei
#14
Johannes Petrus Maree, Megan Lindsay Povelones, David Johannes Clark, Gloria Rudenko, Hugh-George Patterton
BACKGROUND: The compaction of DNA in chromatin in eukaryotes allowed the expansion of genome size and coincided with significant evolutionary diversification. However, chromatin generally represses DNA function, and mechanisms coevolved to regulate chromatin structure and its impact on DNA. This included the selection of specific nucleosome positions to modulate accessibility to the DNA molecule. Trypanosoma brucei, a member of the Excavates supergroup, falls in an ancient evolutionary branch of eukaryotes and provides valuable insight into the organization of chromatin in early genomes...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28331549/dynamics-of-5-methylcytosine-and-5-hydroxymethylcytosine-during-pronuclear-development-in-equine-zygotes-produced-by-icsi
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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