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Andrew A Bartlett, Richard G Hunter
The brain is responsible for both recognition and adaptation to stressful stimuli. Many molecular mechanisms have been implicated in this response including those governing neuronal plasticity, neurogenesis and, changes gene expression. Far less is known regarding effects of stress on the deep genome. In the hippocampus, stress appears to regulate expression of non-coding elements of the genome as well as the chromatin permissive for their transcription. Specifically, hippocampal retrotransposon (RT) elements are regulated by acute stress via the accumulation of the repressive H3K9me3 mark at RT loci...
March 15, 2018: Frontiers in Neuroendocrinology
Louise Rasmussen, Ib Jarle Christensen, Marielle Herzog, Jake Micallef, Hans Jørgen Nielsen
The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC)...
February 13, 2018: Oncotarget
Xian Wang, Shaolei Ma, Haibo Wu, Xiaofeng Shen, Shiqin Xu, Xirong Guo, Maria L Bolick, Shizheng Wu, Fuzhou Wang
Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory...
February 16, 2018: Experimental & Molecular Medicine
Raúl F Pérez, Juan Ramón Tejedor, Gustavo F Bayón, Agustín F Fernández, Mario F Fraga
Cancer is an aging-associated disease, but the underlying molecular links between these processes are still largely unknown. Gene promoters that become hypermethylated in aging and cancer share a common chromatin signature in ES cells. In addition, there is also global DNA hypomethylation in both processes. However, the similarity of the regions where this loss of DNA methylation occurs is currently not well characterized, and it is unknown if such regions also share a common chromatin signature in aging and cancer...
March 5, 2018: Aging Cell
Abdullah Al Emran, Diego M Marzese, Dinoop Ravindran Menon, Mitchell S Stark, Joachim Torrano, Heinz Hammerlindl, Gao Zhang, Patricia Brafford, Matthew P Salomon, Nellie Nelson, Sabrina Hammerlindl, Deepesh Gupta, Gordon B Mills, Yiling Lu, Richard A Sturm, Keith Flaherty, Dave S B Hoon, Brian Gabrielli, Meenhard Herlyn, Helmut Schaider
Besides somatic mutations or drug efflux, epigenetic reprogramming can lead to acquired drug resistance. We recently have identified early stress-induced multi-drug tolerant cancer cells termed induced drug-tolerant cells (IDTCs). Here, IDTCs were generated using different types of cancer cell lines; melanoma, lung, breast and colon cancer. A common loss of the H3K4me3 and H3K27me3 and gain of H3K9me3 mark was observed as a significant response to drug exposure or nutrient starvation in IDTCs. These epigenetic changes were reversible upon drug holidays...
February 2, 2018: Oncotarget
Xinpei Ci, Jun Hao, Xin Dong, Stephen Y C Choi, Hui Xue, Rebecca Wu, Sifeng Qu, Peter W Gout, Fang Zhang, Anne M Haegert, Ladan Fazil, Francesco Crea, Christopher J Ong, Amina Zoubedi, Housheng H He, Martin E Gleave, Colin C Collins, Dong Lin, Yuzhuo Wang
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) arising mostly from adenocarcinoma via NE transdifferentiation following androgen deprivation therapy. Mechanisms contributing to both NEPC development and its aggressiveness remain elusive. In light of the fact that hyperchromatic nuclei are a distinguishing histopathological feature of NEPC, we utilized transcriptomic analyses of our patient-derived xenograft (PDX) models, multiple clinical cohorts, and genetically engineered mouse models to identify 36 heterochromatin-related genes that are significantly enriched in NEPC...
February 27, 2018: Cancer Research
Holly Whitton, Larry N Singh, Marissa A Patrick, Andrew J Price, Fernando G Osorio, Carlos López-Otín, Irina M Bochkis
Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors...
February 27, 2018: Aging Cell
Pamela Prini, Franceso Rusconi, Erica Zamberletti, Marina Gabaglio, Federica Penna, Mauro Fasano, Elena Battaglioli, Daniela Parolaro, Tiziana Rubino
BACKGROUND: Increasing cannabis consumption among adolescents, studies that link its early use with mental illnesses, and the political debate on cannabis legalization together call for an urgent need to study molecular underpinnings of adolescent brain vulnerability. The emerging role of epigenetic mechanisms in psychiatric diseases led us to hypothesize that epigenetic alterations could play a role in causes and subsequent development of the depressive/psychotic-like phenotype induced by adolescent, but not adult, Δ9-tetrahydrocannabinol (THC) exposure in female rats...
March 2018: Journal of Psychiatry & Neuroscience: JPN
Xin Liu, Yizhi Wang, Yuanpeng Gao, Jianmin Su, Jingcheng Zhang, Xupeng Xing, Chuan Zhou, Kezhen Yao, Quanli An, Yong Zhang
Aberrant epigenetic reprogramming often results in developmental defects in somatic cell nuclear transfer (SCNT) embryos during embryonic genome activation (EGA). Bovine eight-cell SCNT embryos exhibit global hypermethylation of histone H3 lysine 9 tri- and di-methylation (H3K9me3/2), but the intrinsic reason for this remains elusive. Here, we provide evidence that two H3K9 demethylase genes, lysine-specific demethylase 4D ( KDM4D ) and 4E ( KDM4E ), are related to active H3K9me3/2 demethylation in in vitro fertilized (IVF) embryos and are deficiently expressed in cloned embryos at the time of EGA...
February 16, 2018: Development
Qi Lv, Kai Wang, Simiao Qiao, Ling Yang, Yirong Xin, Yue Dai, Zhifeng Wei
Norisoboldine (NOR), a natural aryl hydrocarbon receptor (AhR) agonist, has been demonstrated to attenuate ulcerative colitis (UC) and induce the generation of Treg cells. Under UC condition, hypoxia widely exists in colonic mucosa, and secondary changes of microRNAs (miRs) expressions and glycolysis contribute to Treg differentiation. At present, we worked for exploring the deep mechanisms for NOR-promoted Treg differentiation in hypoxia and its subsequent anti-UC action from the angle of AhR/miR or AhR/glycolysis axis...
February 15, 2018: Cell Death & Disease
Michael Hausmann, Emma Wagner, Jin-Ho Lee, Gerrit Schrock, Wladimir Schaufler, Matthias Krufczik, Franziska Papenfuß, Matthias Port, Felix Bestvater, Harry Scherthan
Ionizing radiation (IR)-induced damage confers functional and conformational changes to nuclear chromatin associated with DNA single and double strand breaks. This leads to the activation of complex DNA repair machineries that aim to preserve the integrity of the DNA molecule. Since hetero- and euchromatin are differentially accessible to DNA repair pathways, local chromatin re-arrangements and structural changes are among the consequences of an activated DNA damage response. Using super-resolution localization microscopy (SRLM), we investigated the X-ray-induced repositioning of γ-H2AX and histone H3K9me3 heterochromatin marks in the nuclei of HeLa cells...
February 14, 2018: Nanoscale
Prajakta Khalkar, Hani Abdulkadir Ali, Paula Codó, Nuria Díaz Argelich, Anni Martikainen, Mohsen Karimi Arzenani, Sören Lehmann, Julian Walfridsson, Johanna Ungerstedt, Aristi P Fernandes
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq)...
February 10, 2018: Free Radical Biology & Medicine
Shina Liu, Fei Liu, Weina Huang, Lina Gu, Lingjiao Meng, Yingchao Ju, Yunyan Wu, Juan Li, Lihua Liu, Meixiang Sang
Recently, we have reported that the product of Melanoma Antigens Genes (MAGE) family member MAGE-A11 is an independent poor prognostic marker for esophageal squamous cell carcinoma (ESCC). However, the reason how MAGE-A11 is activated in ESCC progression still remains unclear. In the current study, we demonstrated that DNA methylation and the subsequent histone posttranslational modifications play crucial roles in the regulation of MAGE-A11 in ESCC progression. We found that the methylation rate of TFCP2/ZEB1 binding site on MAGE-A11 promoter in ESCC tissues and cells is higher than the normal esophageal epithelial tissues and cells...
January 9, 2018: Oncotarget
Weiwei Lai, Jiantao Jia, Bin Yan, Yiqun Jiang, Ying Shi, Ling Chen, Chao Mao, Xiaoli Liu, Haosheng Tang, Menghui Gao, Ya Cao, Shuang Liu, Yongguang Tao
Baicalin hydrate (BH), a natural compound, has been investigated for many years because of its traditional medicinal properties. However, the anti-tumor activities of BH and its epigenetic role in NPC have not been elucidated. In this study, we identified that BH inhibits NPC cell growth in vivo and in vitro by inducing apoptosis and cell cycle arrest. BH epigenetically regulated genome instability by up-regulating the expression of satellite 2 (Sat2), alpha satellite (α-Sat), and major satellite (Major-Sat)...
January 2, 2018: Oncotarget
Chunwan Lu, Dafeng Yang, Maria E Sabbatini, Aaron H Colby, Mark W Grinstaff, Nicholas H Oberlies, Cedric Pearce, Kebin Liu
BACKGROUND: Pancreas ductal adenocarcinoma (PDAC) has the most dismal prognosis among all human cancers since it is highly resistant to chemotherapy, radiotherapy and immunotherapy. The anticipated consequence of all therapies is induction of tumor apoptosis. The highly resistance nature of PDACs to all therapies suggests that the intrinsic tumor cell factors, likely the deregulated apoptosis pathway, are key mechanisms underlying PDAC non-response to these therapies, rather than the therapeutic agents themselves...
February 6, 2018: BMC Cancer
Linfeng Gao, Xiao-Feng Tan, Shen Zhang, Tianchen Wu, Zhi-Min Zhang, Hui-Wang Ai, Jikui Song
UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR). Structural analysis reveals that PBR binding leads to displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded UHRF1 conformation...
January 18, 2018: Structure
Zhen Liu, Yijun Cai, Yan Wang, Yanhong Nie, Chenchen Zhang, Yuting Xu, Xiaotong Zhang, Yong Lu, Zhanyang Wang, Muming Poo, Qiang Sun
Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys...
January 20, 2018: Cell
Sanoji Wijenayake, Liam J Hawkins, Kenneth B Storey
The importance of histone lysine methylation is well established in health, disease, early development, aging, and cancer related-research. However, the potential role of epigenetics in regulating gene expression in response to extended periods of oxygen deprivation (anoxia) in a natural anoxia-tolerant model system is underexplored. Red-eared sliders (Trachemys scripta elegans) can tolerate and survive three months of absolute anoxia and recover without incurring detrimental cellular damage, mainly by reducing the overall metabolic rate by 90% when compared to normoxia conditions...
January 27, 2018: Gene
Bo Han, Jinquan Cai, Weida Gao, Xiangqi Meng, Fei Gao, Pengfei Wu, Chunbin Duan, Ruijia Wang, Magafurov Dinislam, Lin Lin, Chunsheng Kang, Chuanlu Jiang
Mutations in ATRX constitute the most prevalent genetic abnormalities in gliomas. The presence of ATRX mutations in glioma serves as a marker of better prognosis with longer patient survival although the underlying mechanisms are poorly understood. In the present study, we found that ATRX biological function was significantly involved in DNA replication and repair. CRISPR/Cas9-mediated genetic inactivation of ATRX induced inhibition of cell proliferation, invasion and vasculogenic mimicry. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in ATRX knockout glioma cells...
January 26, 2018: Cancer Letters
Agnieszka Anna Rawłuszko-Wieczorek, Franziska Knodel, Raluca Tamas, Arunkumar Dhayalan, Albert Jeltsch
BACKGROUND: Protein posttranslational modifications (PTMs) occur broadly in the human proteome, and their biological outcome is often mediated indirectly by reader proteins that specifically bind to modified proteins and trigger downstream effects. Particularly, many lysine methylation sites among histone and nonhistone proteins have been characterized; however, the list of readers associated with them is incomplete. RESULTS: This study introduces a modified yeast three-hybrid system (Y3H) to screen for methyllysine readers...
January 25, 2018: Epigenetics & Chromatin
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