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Epigenetic silencing

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https://www.readbyqxmd.com/read/29350289/small-rna-pathways-responsible-for-non-cell-autonomous-regulation-of-plant-reproduction
#1
REVIEW
Ken-Ichi Nonomura
In angiosperms, germline precursors and germ cells are always attached to or engulfed within somatic companion cells until just before fertilization. This is because sperm and egg cells develop as part of the multicellular gametophyte. Thus, the non-cell-autonomous regulation by somatic companions plays important roles in efficient reproduction, in addition to the cell-autonomous regulation. Epigenetic silencing of transposable elements is one of the central events by which the germline transmits the error-free genome to the next generation...
January 19, 2018: Plant Reproduction
https://www.readbyqxmd.com/read/29345184/temperature-dependent-small-rna-expression-in-drosophila-melanogaster
#2
Isabel Fast, David Rosenkranz
Temperature has a major impact on gene expression in ectotherms. But until recently, it was not clear in which way, if any, small non-coding RNAs such as miRNAs or piRNAs contribute to thermosensitive gene regulation. We have recently shown that temperature-responsive miRNAs in Drosophila drive adaptation to different ambient temperatures on the transcriptome level. Moreover, we demonstrated that higher temperatures lead to a more efficient piRNA-dependent transposon silencing, possibly due to heat-induced unfolding of RNA secondary structures...
January 18, 2018: RNA Biology
https://www.readbyqxmd.com/read/29342143/regulation-of-embryonic-haematopoietic-multipotency-by-ezh1
#3
Linda T Vo, Melissa A Kinney, Xin Liu, Yuannyu Zhang, Jessica Barragan, Patricia M Sousa, Deepak K Jha, Areum Han, Marcella Cesana, Zhen Shao, Trista E North, Stuart H Orkin, Sergei Doulatov, Jian Xu, George Q Daley
All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29341428/epigenetic-silencing-of-tap1-in-aldefluor-breast-cancer-stem-cells-contributes-to-their-enhanced-immune-evasion
#4
Mohammad Sultan, Dejan Vidovic, Arianne S Paine, Thomas T Huynh, Krysta M Coyle, Margaret L Thomas, Brianne M Cruickshank, Cheryl A Dean, Derek R Clements, Youra Kim, Kristin Lee, Shashi A Gujar, Ian C Weaver, Paola Marcato
Avoiding detection and destruction by immune cells is key for tumor initiation and progression. The important role of cancer stem cells (CSC) in tumor initiation has been well established, yet their ability to evade immune detection and targeting is only partly understood. To investigate the ability of breast CSCs to evade immune detection we identified a highly tumorigenic population in a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase (ALDH) activity. We performed tumor growth studies in immunocompetent and immunocompromised mice...
January 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29340787/a-profilin-gene-promoter-from-switchgrass-panicum-virgatum-l-directs-strong-and-specific-transgene-expression-to-vascular-bundles-in-rice
#5
Wenzhi Xu, Wusheng Liu, Rongjian Ye, Mitra Mazarei, Debao Huang, Xinquan Zhang, C Neal Stewart
A switchgrass vascular tissue-specific promoter (PvPfn2) and its 5'-end serial deletions drive high levels of vascular bundle transgene expression in transgenic rice. Constitutive promoters are widely used for crop genetic engineering, which can result in multiple off-target effects, including suboptimal growth and epigenetic gene silencing. These problems can be potentially avoided using tissue-specific promoters for targeted transgene expression. One particularly urgent need for targeted cell wall modification in bioenergy crops, such as switchgrass (Panicum virgatum L...
January 17, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#6
Natalia I Díaz-Valdivia, Claudia C Calderón, Jorge E Díaz, Lorena Lobos-González, Hugo Sepulveda, Rina J Ortíz, Samuel Martinez, Veronica Silva, Horacio J Maldonado, Patricio Silva, Sergio Wehinger, Verónica A Burzio, Vicente A Torres, Martín Montecino, Lisette Leyton, Andrew F G Quest
Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339785/the-lncrna-gata6-as-epigenetically-regulates-endothelial-gene-expression-via-interaction-with-loxl2
#7
Philipp Neumann, Nicolas Jaé, Andrea Knau, Simone F Glaser, Youssef Fouani, Oliver Rossbach, Marcus Krüger, David John, Albrecht Bindereif, Phillip Grote, Reinier A Boon, Stefanie Dimmeler
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here, we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulate endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-β2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339543/genes-predisposed-to-dna-hypermethylation-during-acquired-resistance-to-chemotherapy-are-identified-in-ovarian-tumors-by-bivalent-chromatin-domains-at-initial-diagnosis
#8
Edward Curry, Constanze Zeller, Nahal Masrour, Darren Patten, John Gallon, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D L Bowtell, Robert Brown
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells aberrantly poised genes may facilitate changes in transcriptional states after exposure to anti-cancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339473/identification-of-thioredoxin-interacting-protein-txnip-as-a-downstream-target-for-igf1-action
#9
Karthik Nagaraj, Lena Lapkina-Gendler, Rive Sarfstein, David Gurwitz, Metsada Pasmanik-Chor, Zvi Laron, Shoshana Yakar, Haim Werner
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29337183/temporal-layering-of-signaling-effectors-drives-chromatin-remodeling-during-hair-follicle-stem-cell-lineage-progression
#10
Rene C Adam, Hanseul Yang, Yejing Ge, Wen-Hui Lien, Ping Wang, Yilin Zhao, Lisa Polak, John Levorse, Sanjeethan C Baksh, Deyou Zheng, Elaine Fuchs
Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stem cell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineages. Using enhancer-driven reporters, mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification...
January 9, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29337063/bmi1-activates-wnt-signaling-in-colon-cancer-by-negatively-regulating-the-wnt-antagonist-idax
#11
Feiyue Yu, Chuanyi Zhou, Hui Zeng, Yabing Liu, Shangfu Li
Aberrant activation of Wnt signaling plays a critical role in the development of colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is upregulated in various types of cancer and contributes to epigenetic silencing of tumor suppressors. In this study, we showed that BMI1 is upregulated in colon cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in colon cancer cells represses these effects...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29336876/structural-basis-of-heterochromatin-formation-by-human-hp1
#12
Shinichi Machida, Yoshimasa Takizawa, Masakazu Ishimaru, Yukihiko Sugita, Satoshi Sekine, Jun-Ichi Nakayama, Matthias Wolf, Hitoshi Kurumizaka
Heterochromatin plays important roles in transcriptional silencing and genome maintenance by the formation of condensed chromatin structures, which determine the epigenetic status of eukaryotic cells. The trimethylation of histone H3 lysine 9 (H3K9me3), a target of heterochromatin protein 1 (HP1), is a hallmark of heterochromatin formation. However, the mechanism by which HP1 folds chromatin-containing H3K9me3 into a higher-order structure has not been elucidated. Here we report the three-dimensional structure of the H3K9me3-containing dinucleosomes complexed with human HP1α, HP1β, and HP1γ, determined by cryogenic electron microscopy with a Volta phase plate...
January 10, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29335872/disruptor-of-telomeric-silencing-1-like-dot1l-disclosing-a-new-class-of-non-nucleoside-inhibitors-by-means-of-ligand-based-and-structure-based-approaches
#13
Manuela Sabatino, Dante Rotili, Alexandros Patsilinakos, Mariantonietta Forgione, Daniela Tomaselli, Fréderic Alby, Paola B Arimondo, Antonello Mai, Rino Ragno
Chemical inhibition of chromatin-mediated signaling involved proteins is an established strategy to drive expression networks and alter disease progression. Protein methyltransferases are among the most studied proteins in epigenetics and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine methyltransferase plays a key role in MLL-rearranged acute leukemia Selective inhibition of DOT1L is an established attractive strategy to breakdown aberrant H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis...
January 15, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29334780/rules-governing-the-mechanism-of-epigenetic-reprogramming-memory
#14
Phuc-Loi Luu, Daniela Gerovska, Hans R Schöler, Marcos J Araúzo-Bravo
AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS & METHODS: We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION: Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions...
January 16, 2018: Epigenomics
https://www.readbyqxmd.com/read/29334683/epigenetic-silencing-of-the-mlh1-promoter-in-relation-to-the-development-of-gastric-cancer-and-its-use-as-a-biomarker-for-patients-with-microsatellite-instability-a-systematic-analysis
#15
Guimei Hu, Lijun Qin, Xinjun Zhang, Guoliang Ye, Tao Huang
BACKGROUND/AIMS: Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. METHODS: The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. RESULTS: A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis...
January 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29333921/targeting-brd4-proteins-suppresses-the-growth-of-nsclc-through-downregulation-of-eif4e-expression
#16
Zhongyuan Gao, Ting Yuan, Xiao Zhou, Ping Ni, Geng Sun, Ping Li, Zhixiang Cheng, Xuerong Wang
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29331027/mir-137-functions-as-a-tumor-suppressor-in-pancreatic-cancer-by-targeting-mrgbp
#17
Feng Ding, Shuang Zhang, Shaoyang Gao, Jian Shang, Yanxia Li, Ning Cui, Qiu Zhao
miRNAs are small noncoding RNAs that act as critical epigenetic regulators in tumor carcinogenesis. In this study, our data showed that miR-137 was significantly downregulated in 58 pairs of human pancreatic cancer (PanCa) tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated with increased tumor size, higher TNM stage, and worse prognosis in pancreatic cancer. Functional studies demonstrated that overexpression of miR-137 dramatically suppressed cell proliferation and induced cell apoptosis in vitro...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330773/mechanistic-regulation-of-epithelial-to-mesenchymal-transition-through-ras-signaling-pathway-and-therapeutic-implications-in-human-cancer
#18
REVIEW
Kiran Tripathi, Minal Garg
RAS effector signaling instead of being simple, unidirectional and linear cascade, is actually recognized as highly complex and dynamic signaling network. RAF-MEK-ERK cascade, being at the center of complex signaling network, links to multiple scaffold proteins through feed forward and feedback mechanisms and dynamically regulate tumor initiation and progression. Three isoforms of Ras harbor mutations in a cell and tissue specific manner. Besides mutations, their epigenetic silencing also attributes them to exhibit oncogenic activities...
January 12, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#19
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29327713/expression-of-enhancer-of-zeste-homolog-2-ezh2-protein-in-histiocytic-and-dendritic-cell-neoplasms-with-evidence-for-p-erk1-2-related-but-not-myc-or-p-stat3-related-cell-signaling
#20
Xuejun Tian, Jie Xu, Christopher Fletcher, Jason L Hornick, David M Dorfman
EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb repressive complex 2 (PRC2), which controls gene silencing through post-translational modification, and is overexpressed in various carcinomas and hematopoietic neoplasms. We found that the majority of cases of histiocytic and dendritic cell neoplasms, including histiocytic sarcoma, follicular dendritic cell sarcoma, Langerhans cell histiocytosis, and interdigitating dendritic cell sarcoma, show strong EZH2 expression by immunohistochemical staining, in contrast to benign histiocytic lesions and normal cellular counterparts, which did not show EZH2 expression, suggesting that this molecule may function as an oncogenic protein in these neoplasms...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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