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Houliang Deng, Jianming Zeng, Ting Zhang, Longcai Gong, Hongjie Zhang, Edwin Cheung, Chris Jones, Gang Li
Lysine to Methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 (PRC2) and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drive the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatric HGG development driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3...
February 16, 2018: Molecular Cancer Research: MCR
Wenyong Long, Wei Zhao, Bo Ning, Jing Huang, Junjun Chu, Linfeng Li, Qianquan Ma, Changsheng Xing, Helen Y Wang, Qing Liu, Rong-Fu Wang
The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of stemness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Cas9-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. Expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients...
February 14, 2018: Journal of Molecular Cell Biology
Harshavardhan Janga, Marina Aznaourova, Fabian Boldt, Katrin Damm, Arnold Grünweller, Leon N Schulte
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes...
2018: PloS One
Céline Adam, Raphaël Guérois, Anna Citarella, Laura Verardi, Florine Adolphe, Claire Béneut, Vérane Sommermeyer, Claire Ramus, Jérôme Govin, Yohann Couté, Valérie Borde
Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double-strand break (DSB) formation that in budding yeast takes place in gene promoters and is promoted by histone H3K4 di/trimethylation. This histone modification is recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me3 and interacts with a DSB protein, Mer2, to promote DSB formation close to gene promoters...
February 14, 2018: PLoS Genetics
Pengfei Jiang, Shiliang Wang, Haiyang Jiang, Beijiu Cheng, Keqiang Wu, Yong Ding
Flowering time (heading date) and panicle branch number are important agronomic traits that determine yield in rice (Oryza sativa). The activation of flowering requires histone methylation, but the roles of tri-methylation of lysine 4 of histone 3 (H3K4me3) in modulating heading date and panicle development are unclear. Here, we showed that the COMPASS-like complex promotes flowering and panicle branching. The rice WD40 protein OsWDR5a interacts with the TRITHORAX-like protein OsTrx1/SDG723 to form the core components of the COMPASS-like complex...
February 12, 2018: Plant Physiology
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
Kelly Maurer, Swathi Ramen, Lihuaa Shi, Li Song, Kathleen E Sullivan
The response to infection is managed in mammals by a coordinated immune response. Innate responses are rapid and hard wired and have been demonstrated to be regulated at the level of chromatin accessibility. This study examined primary human monocyte responses to LPS as a model of innate responses to bacteria. We utilized inhibitors of chromatin modifying enzymes to understand the inter-relationships of the chromatin complexes regulating transcription. Multiplex digital gene detection was utilized to quantitate changes in mRNA levels for genes induced by LPS...
February 9, 2018: Molecular Immunology
Myriam Koubi, Mathilde Poplineau, Julien Vernerey, Lia N'Guyen, Guillaume Tiberi, Sylvain Garciaz, Abdessamad El-Kaoutari, Muhammad A Maqbool, Jean-Christophe Andrau, Christel Guillouf, Andrew J Saurin, Estelle Duprez
The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level...
February 7, 2018: Nucleic Acids Research
Yipeng Sui, Se-Hyung Park, Fang Wang, Changcheng Zhou
Bisphenol A (BPA) is a base chemical used extensively in numerous consumer products, and human exposure to BPA is ubiquitous. Higher BPA exposure has been associated with increased risk of atherosclerosis and cardiovascular disease (CVD) in multiple human population-based studies, but the underlying mechanisms responsible for the associations remain elusive. We previously reported that BPA activates the xenobiotic receptor pregnane X receptor (PXR) which has pro-atherogenic effects in animal models. Since BPA is a potent agonist for human PXR but does not affect rodent PXR activity, a suitable PXR-humanized Apolipoprotein E-deficient (huPXR•ApoE-/-) mouse model was developed to study BPA's atherogenic effects, and chronic BPA exposure indeed increased atherosclerosis in huPXR•ApoE-/- mice...
February 7, 2018: Endocrinology
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
Yanjian Li, Yi He, Zhengyu Liang, Yang Wang, Fengling Chen, Mohamed Nadhir Djekidel, Guipeng Li, Xu Zhang, Shuqin Xiang, Zejun Wang, Juntao Gao, Michael Q Zhang, Yang Chen
Chromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chromatin accessibility, and gene expression using an all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation model. The results showed that the boundaries of topological associated domains (TADs) were stable during differentiation; however, the chromatin conformations within several specific TADs were obviously changed...
February 8, 2018: Cell Death & Disease
Qi-Fan Zheng, Bin Xu, Hui-Min Wang, Li-Hong Ding, Jin-Yang Liu, Ling-Yu Zhu, Huan Qiu, Li Zhang, Guang-Yi Ni, Jing Ye, Shu-Bin Gao, Guang-Hui Jin
The expression of insulin-like growth factor 2 (IGF2), a classical imprinting gene, didn't completely correlate with its imprinting profiles in hepatocellular carcinoma (HCC). The mechanistic importance of promoter activity in regulation of IGF2 has not been fully clarified. Here we show that histone 3 lysine 4 trimethylation (H3K4me3) modified by menin-MLL complex of IGF2 promoter contributes to promoter activity of IGF2. The strong binding of menin and abundant H3K4me3 at the DNA demethylated P3/4 promoters were observed in Hep3B cells with the robust expression of IGF2...
January 31, 2018: Biochimica et Biophysica Acta
Himanshu Agrawal, Naresh Lalaji Selokar, Monika Saini, Manoj Kumar Singh, Manmohan Singh Chauhan, Prabhat Palta, Suresh Kumar Singla, Radhey Sham Manik
Epigenetic reprogramming is an indispensable process during the course of mammalian development, but aberrant in cloned embryos. The aim of this study was to examine the effect of donor cell treatment with histone deacetylase (HDAC) inhibitor m-carboxycinnamic acid bishydroxymide (CBHA) on cloned embryo development and establish its optimal concentration. Different concentrations of CBHA (2.5, 5.0, 10.0, and 20.0 μM) were used to treat buffalo adult fibroblast cells for 24 hours and effect on cell proliferation, gene expression, and histone modifications was analyzed...
February 2018: Cellular Reprogramming
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
Shangrong Wu, Nana Han, Yong Zheng, Chengjun Hu, Yueshan Lei
The osteogenic capacities of bone marrow-derived stromal cells (BMSCs) diminish during replicative senescence, and these changes affect the success of therapeutic application of BMSCs. In this study, we sought to explore the molecular mechanisms underlying the osteogenic differentiation capacities that occur during replicative senescence. It is well known that Oct4 is a key transcription factor essential for maintaining differentiation capacities of the stem cells. In this study, we found that BMSCs at passage 6 (replicative senescent BMSCs) showed marked decreases in the osteogenic differentiation potential and the level of Oct4...
February 1, 2018: Mechanisms of Ageing and Development
Jia Li, Xinwei Wu, Yubin Zhou, Minjung Lee, Lei Guo, Wei Han, William Mo, Wen-Ming Cao, Deqiang Sun, Ruiyu Xie, Yun Huang
Dynamic changes in DNA methylation and demethylation reprogram transcriptional outputs to instruct lineage specification during development. Here, we applied an integrative epigenomic approach to unveil DNA (hydroxy)methylation dynamics representing major endodermal lineage intermediates during pancreatic differentiation of human embryonic stem cells (hESCs). We found that 5-hydroxymethylcytosine (5hmC) marks genomic regions to be demethylated in the descendent lineage, thus reshaping the DNA methylation landscapes during pancreatic lineage progression...
January 31, 2018: Nucleic Acids Research
Kaj Chokeshaiusaha, Denis Puthier, Catherine Nguyen, Thanida Sananmuang
Objective: Trimethylation of histone 3 (H3) at 4th lysine N-termini (H3K4me3) in gene promoter region was the universal marker of active genes specific to cell lineage. On the contrary, coexistence of trimethylation at 27th lysine (H3K27me3) in the same loci-the bivalent H3K4m3/H3K27me3 was known to suspend the gene transcription in germ cells, and could also be inherited to the developed stem cell. In galline species, throughout example of H3K4m3 and H3K27me3 ChIP-seq analysis was still not provided...
January 26, 2018: Asian-Australasian Journal of Animal Sciences
Urszula L McClurg, Arash Nabbi, Charles Ricordel, Svitlana Korolchuk, Stuart McCracken, Rakesh Heer, Laura Wilson, Lisa M Butler, Bronwyn Kate Irving-Hooper, Rémy Pedeux, Craig N Robson, Karl T Riabowol, Olivier Binda
BACKGROUND: Although the founding members of the INhibitor of Growth (ING) family of histone mark readers, ING1 and ING2, were defined as tumour suppressors in animal models, the role of other ING proteins in cellular proliferation and cancer progression is unclear. METHODS: We transduced ex vivo benign prostate hyperplasia tissues with inducible lentiviral particles to express ING proteins. Proliferation was assessed by H3S10phos immunohistochemistry (IHC). The expression of ING3 was assessed by IHC on a human prostate cancer tissue microarray (TMA)...
January 30, 2018: British Journal of Cancer
Mingli Xu, Aaron R Leichty, Tieqiang Hu, R Scott Poethig
Vegetative phase change in Arabidopsis thaliana is mediated by a decrease in the level of MIR156A and MIR156C, resulting in an increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes. Changes in chromatin structure are required for the downregulation of MIR156A and MIR156C, but whether chromatin structure contributes to their initial elevated expression is unknown. We found that mutations in components of the SWR1 complex (ARP6, SEF) and in genes encoding H2A.Z (HTA9 and HTA11) reduce the expression of MIR156A and MIR156C, and accelerate vegetative phase change, indicating that H2A...
January 25, 2018: Development
Hao Zhang, Qian-Yun He, Guang-Chao Wang, Da-Ke Tong, Ren-Kai Wang, Wen-Bin Ding, Cheng Li, Qiang Wei, Chen Ding, Pei-Zhao Liu, Hao-Chen Cui, Xin Zhang, Di Li, Hao Tang, Fang Ji
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. However, the underlying mechanism of osteosarcoma carcinogenesis and progression remains unknown. In the present study, we evaluated the expression profile of miRNAs in osteosarcoma tissues and the adjacent normal tissues. We found that the expression of miR-422a was down-regulated in osteosarcoma tissues and cell lines. In addition, we observed significantly elevated levels of repressive H3K9me3 and H3K27me3 and decreased active H3K4me3 on the promote region of miR-422a in osteosarcoma cells and clinical samples...
January 22, 2018: Bioscience Reports
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