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Epigenetics and h2b

Hui Shen, Yuwei Zhu, Chongyuan Wang, Hui Yan, Maikun Teng, Xu Li
Hda1 is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Though the N-terminal catalytic HDAC domain of Hda1 is well characterized, the function of the C-terminal ARB2 domain remains unknown. In this study, we determine the crystal structure of the ARB2 domain from S. cerevisiae Hda1 at a resolution of 2.7 Å...
September 26, 2016: Scientific Reports
Anna Török, Philipp H Schiffer, Christine E Schnitzler, Kris Ford, James C Mullikin, Andreas D Baxevanis, Antony Bacic, Uri Frank, Sebastian G Gornik
BACKGROUND: Cnidarians are a group of early branching animals including corals, jellyfish and hydroids that are renowned for their high regenerative ability, growth plasticity and longevity. Because cnidarian genomes are conventional in terms of protein-coding genes, their remarkable features are likely a consequence of epigenetic regulation. To facilitate epigenetics research in cnidarians, we analysed the histone complement of the cnidarian model organism Hydractinia echinata using phylogenomics, proteomics, transcriptomics and mRNA in situ hybridisations...
2016: Epigenetics & Chromatin
Santosh Kumar Goru, Almesh Kadakol, Anuradha Pandey, Vajir Malek, Nisha Sharma, Anil Bhanudas Gaikwad
Hyperglycaemia-induced expression of extracellular matrix (ECM) components plays a major role in the development diabetic nephropathy (DN). The epigenetic mechanisms that modulate ECM gene expression in DN remain unclear. Therefore, we examined the role of histone H2A and H2B mono-ubiquitination on epigenetic chromatin marks such as histone H3 lysine dimethylation (H3K4Me2, H3K9Me2 and H3K79Me2) in type 1 diabetic rat kidney. Hyperglycaemia increased collagen deposition and Col1a1 gene expression. In whole kidney of diabetic animals, both H2AK119 mono-ubiquitination (H2AK119Ub) and H2BK120 mono-ubiquitination (H2BK120Ub) were found to be increased whereas, in glomeruli of diabetic animals expression of both H2AK119Ub and H2BK120Ub were reduced...
August 31, 2016: Biochemical Journal
Zachary S Bailey, Michael B Grinter, Pamela J VandeVord
Blast induced neurotrauma (BINT) is a prevalent injury within military and civilian populations. The injury is characterized by persistent inflammation at the cellular level which manifests as a multitude of cognitive and functional impairments. Epigenetic regulation of transcription offers an important control mechanism for gene expression and cellular function which may underlie chronic inflammation and result in neurodegeneration. We hypothesize that altered histone acetylation patterns may be involved in blast induced inflammation and the chronic activation of glial cells...
2016: Frontiers in Molecular Neuroscience
Jongseong Kim, Sijie Wei, Jaehyoun Lee, Hongjun Yue, Tae-Hee Lee
Structural dynamics of a protein molecule is often critical to its function. Single-molecule methods provide efficient ways to investigate protein dynamics, although it is very challenging to achieve a millisecond or higher temporal resolution. Here we report spontaneous structural dynamics of the histone protein core in the nucleosome based on a single-molecule method that can reveal submillisecond dynamics by combining maximum likelihood estimation and fluorescence correlation spectroscopy. The nucleosome, comprising ∼147 bp DNA and an octameric histone protein core consisting of H2A, H2B, H3, and H4, is the fundamental packing unit of the eukaryotic genome...
September 1, 2016: Journal of Physical Chemistry. B
Sang Ah Yi, Jihoon Han, Jeung-Whan Han
S6K1 is a key regulator of cell growth, cell size, and metabolism. Although the role of cytosolic S6K1 in cellular processes is well established, the function of S6K1 in the nucleus remains poorly understood. Our recent study has revealed that S6K1 is translocated into the nucleus upon adipogenic stimulus where it directly binds to and phosphorylates H2B at serine 36. Such phosphorylation promotes EZH2 recruitment and subsequent histone H3K27 trimethylation on the promoter of its target genes including Wnt6, Wnt10a, and Wnt10b, leading to repression of their expression...
August 2016: BMB Reports
Keng-Po Lai, Jing-Woei Li, Christine Ying-Shan Chan, Ting-Fung Chan, Karen Wing-Yee Yuen, Jill Man-Ying Chiu
Hypoxia occurs when dissolved oxygen (DO) falls below 2.8mgL(-1) in aquatic environments. It can cause trans-generational effects not only in fish, but also in the water fleas Daphnia. In this study, transcriptome sequencing analysis was employed to identify transcriptomic alterations induced by hypoxia in embryos of Daphnia magna, with an aim to investigate the mechanism underlying the trans-generational effects caused by hypoxia in Daphnia. The embryos (F1) were collected from adults (F0) that were previously exposed to hypoxia (or normoxia) for their whole life...
August 2016: Aquatic Toxicology
Øystein Helland, Mihaela Popa, Katharina Bischof, Bjørn Tore Gjertsen, Emmet McCormack, Line Bjørge
BACKGROUND: In most epithelial ovarian carcinomas (EOC), epigenetic changes are evident, and overexpression of histone deacetylases (HDACs) represents an important manifestation. In this study, we wanted to evaluate the effects of the novel HDAC inhibitor (HDACi) panobinostat, both alone and in combination with carboplatin, on ovarian cancer cell lines and in a murine bioluminescent orthotopic surgical xenograft model for EOC. METHODS: The effects of panobinostat, both alone and in combination with carboplatin, on proliferation and apoptosis in ovarian cancer cell lines, were evaluated using colony and WST-1 assays, Hoechst staining and flow cytometry analysis...
2016: PloS One
Lacey J Luense, Xiaoshi Wang, Samantha B Schon, Angela H Weller, Enrique Lin Shiao, Jessica M Bryant, Marisa S Bartolomei, Christos Coutifaris, Benjamin A Garcia, Shelley L Berger
BACKGROUND: During the process of spermatogenesis, male germ cells undergo dramatic chromatin reorganization, whereby most histones are replaced by protamines, as part of the pathway to compact the genome into the small nuclear volume of the sperm head. Remarkably, approximately 90 % (human) to 95 % (mouse) of histones are evicted during the process. An intriguing hypothesis is that post-translational modifications (PTMs) decorating histones play a critical role in epigenetic regulation of spermatogenesis and embryonic development following fertilization...
2016: Epigenetics & Chromatin
Denis Jullien, Julien Vignard, Yoann Fedor, Nicolas Béry, Aurélien Olichon, Michèle Crozatier, Monique Erard, Hervé Cassard, Bernard Ducommun, Bernard Salles, Gladys Mirey
Chromatin function is involved in many cellular processes, its visualization or modification being essential in many developmental or cellular studies. Here, we present the characterization of chromatibody, a chromatin-binding single-domain, and explore its use in living cells. This non-intercalating tool specifically binds the heterodimer of H2A-H2B histones and displays a versatile reactivity, specifically labeling chromatin from yeast to mammals. We show that this genetically encoded probe, when fused to fluorescent proteins, allows non-invasive real-time chromatin imaging...
July 1, 2016: Journal of Cell Science
Jasmine Li, Kristine Hardy, Chan Phetsouphanh, Wen Juan Tu, Elissa L Sutcliffe, Robert McCuaig, Christopher R Sutton, Anjum Zafar, C Mee Ling Munier, John J Zaunders, Yin Xu, Angelo Theodoratos, Abel Tan, Pek Siew Lim, Tobias Knaute, Antonia Masch, Johannes Zerweck, Vedran Brezar, Peter J Milburn, Jenny Dunn, Marco G Casarotto, Stephen J Turner, Nabila Seddiki, Anthony D Kelleher, Sudha Rao
Memory T cells are characterized by their rapid transcriptional programs upon re-stimulation. This transcriptional memory response is facilitated by permissive chromatin, but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4(+) T cells, here, we show that the signaling enzyme, protein kinase C theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to transcriptional-memory-responsive genes to induce transcriptional activation...
June 15, 2016: Journal of Cell Science
Hayretin Yumerefendi, Andrew Michael Lerner, Seth Parker Zimmerman, Klaus Hahn, James E Bear, Brian D Strahl, Brian Kuhlman
We engineered a photoactivatable system for rapidly and reversibly exporting proteins from the nucleus by embedding a nuclear export signal in the LOV2 domain from phototropin 1. Fusing the chromatin modifier Bre1 to the photoswitch, we achieved light-dependent control of histone H2B monoubiquitylation in yeast, revealing fast turnover of the ubiquitin mark. Moreover, this inducible system allowed us to dynamically monitor the status of epigenetic modifications dependent on H2B ubiquitylation.
June 2016: Nature Chemical Biology
Jimmy El Hokayem, George C Brittain, Zafar Nawaz, John R Bethea
The tumor necrosis factor receptor-associated factors (TRAFs) have been classically described as adaptor proteins that function as solely cytosolic signaling intermediates for the TNF receptor superfamily, Toll-like receptors (TLRs), NOD, like receptors (NLRs), cytokine receptors, and others. In this study, we show for the first time that TRAFs are present within the cytoplasm and nucleus of Neuro2a cells and primary cortical neurons, and that TRAF2 and TRAF3 translocate into the nucleus within minutes of CD40L stimulation...
February 3, 2016: Molecular Neurobiology
Iwen Fu, Yuqin Cai, Yingkai Zhang, Nicholas E Geacintov, Suse Broyde
Errors in epigenetic markings are associated with human diseases, including cancer. We have used molecular dynamics simulations of a nucleosome containing the 10S (+)-trans-anti-B[a]P-N(2)-dG lesion, derived from the environmental pro-carcinogen benzo[a]pyrene, to elucidate the impact of the lesion on the structure and dynamics of a nearby histone N-terminal tail. Our results show that a lysine-containing part of this H2B tail that is subject to post-translational modification is engulfed by the enlarged DNA minor groove imposed by the lesion...
January 19, 2016: Biochemistry
Kyle W Anderson, Illarion V Turko
BACKGROUND: Alzheimer's disease (AD) is the sixth leading cause of death and the most costly disease in the US. Despite the enormous impact of AD, there are no treatments that delay onset or stop disease progression currently on the market. This is partly due to the complexity of the disease and the largely unknown pathogenesis of sporadic AD, which accounts for the vast majority of cases. Epigenetics has been implicated as a critical component to AD pathology and a potential "hot spot" for treatments...
2015: Clinical Proteomics
Torunn Rønningen, Akshay Shah, Anja R Oldenburg, Kristin Vekterud, Erwan Delbarre, Jan Øivind Moskaug, Philippe Collas
Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction...
December 2015: Genome Research
Lukas Lercher, Ritu Raj, Nisha A Patel, Joshua Price, Shabaz Mohammed, Carol V Robinson, Christopher J Schofield, Benjamin G Davis
O-GlcNAcylation is a newly discovered histone modification implicated in transcriptional regulation, but no structural information on the physical effect of GlcNAcylation on chromatin exists. Here, we generate synthetic, pure GlcNAcylated histones and nucleosomes and reveal that GlcNAcylation can modulate structure through direct destabilization of H2A/H2B dimers in the nucleosome, thus promoting an 'open' chromatin state. The results suggest that a plausible molecular basis for one role of histone O-GlcNAcylation in epigenetic regulation is to lower the barrier for RNA polymerase passage and hence increase transcription...
2015: Nature Communications
Hong Cao, Xiaoying Li, Zhi Wang, Meng Ding, Yongzhen Sun, Fengqin Dong, Fengying Chen, Li'an Liu, James Doughty, Yong Li, Yong-Xiu Liu
Histone H2B monoubiquitination (H2Bub1) is an important regulatory mechanism in eukaryotic gene transcription and is essential for normal plant development. However, the function of H2Bub1 in reproductive development remains elusive. Here, we report rice (Oryza sativa) HISTONE MONOUBIQUITINATION1 (OsHUB1) and OsHUB2, the homologs of Arabidopsis (Arabidopsis thaliana) HUB1 and HUB2 proteins, which function as E3 ligases in H2Bub1, are involved in late anther development in rice. oshub mutants exhibit abnormal tapetum development and aborted pollen in postmeiotic anthers...
August 2015: Plant Physiology
Shweta R Nayak, Emily Harrington, David Boone, Ryan Hartmaier, Jian Chen, Thushangi N Pathiraja, Kristine L Cooper, Jeffrey L Fine, Joseph Sanfilippo, Nancy E Davidson, Adrian V Lee, David Dabbs, Steffi Oesterreich
Acquired resistance to aromatase inhibitors (AIs) remains a major clinical problem in the treatment of estrogen receptor-positive (ER+) breast cancer. We and others have previously reported widespread changes in DNA methylation using breast cancer cell line models of endocrine resistance. Here, we show that the histone variant HIST1H2BE is hypomethylated in estrogen deprivation-resistant C4-12 and long-term estrogen-deprived (LTED) cells compared with parental MCF-7 cells. As expected, this hypomethylation associates with increased expression of HIST1H2BE in C4-12 and LTED cells...
December 2015: Hormones & Cancer
Tetsuya Fukuda, Hiroshi Hike, Fumihiko Usui, Yasuhiko Bando, Toshihide Nishimura, Tatsuhiko Kodama, Takeshi Kawamura
Highly protonated histone-derived peptides impede a sufficient mass spectrometry (MS)-based epigenetic analysis because their relatively low m/z, due to a high degree of proton addition to peptides, would make it difficult to analyze the resulting complex MS/MS spectra. To reduce the degree of protonations, we have developed a new interface, the Ionization Variable Unit (IVU), in which peptides are ionized under a vaporized organic solvent. It is demonstrated that the doubly charged histone tail H2B peptide, PEPAKSAPAPKKGSKKAVTKAQKK (m/z 1238...
October 1, 2015: Analytical Biochemistry
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