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Small molecule epigenetics

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https://www.readbyqxmd.com/read/29444131/chromatin-immunoprecipitation-improvements-for-the-processing-of-small-frozen-pieces-of-adipose-tissue
#1
Daniel Castellano-Castillo, Pierre-Damien Denechaud, Isabel Moreno-Indias, Francisco Tinahones, Lluis Fajas, María Isabel Queipo-Ortuño, Fernando Cardona
Chromatin immunoprecipitation (ChIP) has gained importance to identify links between the genome and the proteome. Adipose tissue has emerged as an active tissue, which secretes a wide range of molecules that have been related to metabolic and obesity-related disorders, such as diabetes, cardiovascular failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the importance in discerning the possible relationship between metabolic disorders, lifestyle and environment. However, ChIP application in human adipose tissue is limited by several factors, such as sample size, frozen sample availability, high lipid content and cellular composition of the tissue...
2018: PloS One
https://www.readbyqxmd.com/read/29441447/transcriptional-mechanisms-of-secondary-fracture-healing
#2
REVIEW
Joseph L Roberts, David N Paglia, Hicham Drissi
PURPOSE OF REVIEW: Growing evidence supports the critical role of transcriptional mechanisms in promoting the spatial and temporal progression of bone healing. In this review, we evaluate and discuss new transcriptional and post-transcriptional regulatory mechanisms of secondary bone repair, along with emerging evidence for epigenetic regulation of fracture healing. RECENT FINDINGS: Using the candidate gene approach has identified new roles for several transcription factors in mediating the reactive, reparative, and remodeling phases of fracture repair...
February 13, 2018: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29441145/epigenetic-regulation-of-hiv-1-latency-focus-on-polycomb-group-pcg-proteins
#3
REVIEW
Sheraz Khan, Mazhar Iqbal, Muhammad Tariq, Shahid M Baig, Wasim Abbas
HIV-1 latency allows the virus to persist until reactivation, in a transcriptionally silent form in its cellular reservoirs despite the presence of effective cART. Such viral persistence represents a major barrier to HIV eradication since treatment interruption leads to rebound plasma viremia. Polycomb group (PcG) proteins have recently got a considerable attention in regulating HIV-1 post-integration latency as they are involved in the repression of proviral gene expression through the methylation of histones...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29437854/bet-proteins-exhibit-transcriptional-and-functional-opposition-in-the-epithelial-to-mesenchymal-transition
#4
Guillaume P Andrieu, Gerald V Denis
Transcriptional programs in embryogenesis and cancer, such as the epithelial-to-mesenchymal transition (EMT), ensure cellular plasticity, an essential feature of carcinoma progression. As effectors of signal transduction, the bromodomain and extraterminal (BET) proteins are well suited to support plasticity because they function as co-activators or co-repressors of mammalian transcriptomes. Here, using both hormone-sensitive and triple-negative breast cancer (TNBC) model systems, we systematically altered EMT transcriptional profiles by manipulating individual BET proteins and found that BRD2 positively regulates EMT, whereas BRD3 and BRD4 repress this program...
February 7, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29431744/a-histone-deacetylase-3-dependent-pathway-delimits-peripheral-myelin-growth-and-functional-regeneration
#5
Xuelian He, Liguo Zhang, Luis F Queme, Xuezhao Liu, Andrew Lu, Ronald R Waclaw, Xinran Dong, Wenhao Zhou, Grahame Kidd, Sung-Ok Yoon, Andres Buonanno, Joshua B Rubin, Mei Xin, Klaus-Armin Nave, Bruce D Trapp, Michael P Jankowski, Q Richard Lu
Deficits in Schwann cell-mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29425339/cd28-co-stimulation-is-dispensable-for-the-steady-state-homeostasis-of-intestinal-regulatory-t-cells
#6
Ei Wakamatsu, Hiroki Omori, Yuki Tabata, Yuki Akieda, Shiho Watanabe, Shuhei Ogawa, Ryo Abe
It is well-established that CD28 co-stimulation is required for the development and the proliferation of thymus-derived regulatory T cells (tTregs). Meanwhile, the role of CD28 co-stimulation in the homeostasis of peripherally-derived Tregs (pTregs) remains unclear. To clarify this issue, we analyzed Tregs in small and large intestines (SI and LI), the principle sites of pTreg development. Interestingly, and different from in the thymus, Tregs were abundant in the intestines of CD28-/- mice, and most of them were phenotypically pTregs...
February 7, 2018: International Immunology
https://www.readbyqxmd.com/read/29423045/ovatodiolide-targets-chronic-myeloid-leukemia-stem-cells-by-epigenetically-upregulating-hsa-mir-155-suppressing-the-bcr-abl-fusion-gene-and-dysregulating-the-pi3k-akt-mtor-pathway
#7
Yue-Xing Tu, Shi-Bing Wang, Luo-Qin Fu, Shuang-Shuang Li, Qian-Peng Guo, Yi Wu, Xiao-Zhou Mou, Xiang-Min Tong
Chronic myeloid leukemia (CML) is a myeloproliferative pathology, originating from the hematopoietic cancer stem cells (hCSCs) due to the Bcl-Abl Philadelphia chromosome transformation. However, targeting these hCSCs as an effective anti-CML strategy is relatively less explored. Ovatodiolide (Ova) is a natural diterpenoid isolate of Anisomeles indica with broad anticancer activity. In this study, we investigated the anti-hCSCs potential of Ova against CD34+/CD38-, CD34+/CD38+, and unsorted K562 cell lines using flow cytometry, western blot, RT-PCR, genomic mapping, and tumorsphere formation assays...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29400649/train-transcription-of-repeats-activates-interferon-in-response-to-chromatin-destabilization-induced-by-small-molecules-in-mammalian-cells
#8
Katerina Leonova, Alfiya Safina, Elimelech Nesher, Poorva Sandlesh, Rachel Pratt, Catherine Burkhart, Brittany Lipchick, Ilya Gitlin, Costakis Frangou, Igor Koman, Jianmin Wang, Kirill Kirsanov, Marianna G Yakubovskaya, Andrei V Gudkov, Katerina Gurova
Cellular Responses to the loss of genomic stability are well-established, while how mammalian cells respond to chromatin destabilization is largely unknown. We previously found that DNA demethylation on p53-deficient background leads to transcription of repetitive heterochromatin elements, followed by an interferon response, a phenomenon we named TRAIN (Transcription of Repeats Activates INterferon). Here, we report that curaxin, an anticancer small molecule, destabilizing nucleosomes via disruption of histone/DNA interactions, also induces TRAIN...
February 5, 2018: ELife
https://www.readbyqxmd.com/read/29388209/the-role-of-the-mir-200-family-in-epithelial-mesenchymal-transition-in-colorectal-cancer-a-systematic-review
#9
Stephen J O'Brien, Jane V Carter, James F Burton, Brent G Oxford, Miranda N Schmidt, Jacob C Hallion, Susan Galandiuk
Colorectal cancer is associated with significant morbidity and mortality as many patients are diagnosed with advanced stage disease. MicroRNAs are small, non-coding RNA molecules which have a major role in gene expression regulation and are dysregulated in colorectal cancer. The miR-200 family is involved in epithelial-to-mesenchymal transition (EMT). This systematic review describes the roles of the miR-200 family in EMT in colorectal cancer. A search of electronic databases (PubMed and Embase) was conducted between January 2000 and July 2017...
January 31, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29385079/advances-in-the-development-of-pet-ligands-targeting-histone-deacetylases-for-the-assessment-of-neurodegenerative-diseases
#10
REVIEW
Tetsuro Tago, Jun Toyohara
Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs), which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the details of the interaction between changes in HDAC levels in the brain and disease progression remain unknown. In this review, we focus on recent advances in development of radioligands for HDAC imaging in the brain with positron emission tomography (PET)...
January 31, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29381073/synthetic-molecule-protein-hybrid-probe-with-fluorogenic-switch-for-live-cell-imaging-of-dna-methylation
#11
Yuichiro Hori, Norimichi Otomura, Ayuko Nishida, Miyako Nishiura, Maho Umeno, Isao Suetake, Kazuya Kikuchi
Hybrid probes consisting of synthetic molecules and proteins are powerful tools for detecting biological molecules and signals in living cells. To date, most targets of the hybrid probes have been limited to pH and small analytes. Although biomacromolecules are essential to the physiological function of cells, the hybrid-probe-based approach has been scarcely employed for live-cell detection of biomacromolecules. Here, we developed a hybrid probe with a chemical switch for live-cell imaging of methylated DNA, an important macromolecule in the repression of gene expression...
January 30, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29374363/non-coding-rnas-epigenetics-and-cancer-tying-it-all-together
#12
Humberto J Ferreira, Manel Esteller
While only a small part of the human genome encodes for proteins, biological functions for the so-called junk genome are increasingly being recognized through high-throughput technologies and mechanistic experimental studies. Indeed, novel mechanisms of gene regulation are being discovered that require coordinated interaction between DNA, RNA, and proteins. Therefore, interdisciplinary efforts are still needed to decipher these complex transcriptional networks. In this review, we discuss how non-coding RNAs (ncRNAs) are epigenetically regulated in cancer and metastases and consequently how ncRNAs participate in the sculpting of the epigenetic profile of a cancer cell, thus modulating the expression of other RNA molecules...
January 26, 2018: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29355841/jak2-idh-mutant-driven-myeloproliferative-neoplasm-is-sensitive-to-combined-targeted-inhibition
#13
Anna Sophia McKenney, Allison N Lau, Amritha Varshini Hanasoge Somasundara, Barbara Spitzer, Andrew M Intlekofer, Jihae Ahn, Kaitlyn Shank, Franck T Rapaport, Minal A Patel, Efthymia Papalexi, Alan H Shih, April Chiu, Elizaveta Freinkman, Esra A Akbay, Mya Steadman, Raj Nagaraja, Katharine Yen, Julie Teruya-Feldstein, Kwok-Kin Wong, Raajit Rampal, Matthew G Vander Heiden, Craig B Thompson, Ross L Levine
Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617F and mutant IDH1R132H or Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617F Idh2R140Q-mutant MPNs were sensitive to small-molecule inhibition of IDH...
February 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29348610/the-histone-methyltransferase-dot1l-inhibits-osteoclastogenesis-and-protects-against-osteoporosis
#14
Yanpan Gao, Wei Ge
Osteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL-induced RAW264.7 macrophage cells as an osteoclast differentiation model, we found that DOT1L and H3K79me2 levels were upregulated during osteoclast differentiation...
January 18, 2018: Cell Death & Disease
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
#15
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
https://www.readbyqxmd.com/read/29325547/paracrine-and-epigenetic-control-of-caf-induced-metastasis-the-role-of-hotair-stimulated-by-tgf-%C3%A3-1-secretion
#16
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29313325/development-of-a-mirna-surface-enhanced-raman-scattering-assay-using-benchtop-and-handheld-raman-systems
#17
Monika Schechinger, Haley Marks, Andrea Locke, Mahua Choudhury, Gerard Cote
DNA-functionalized nanoparticles, when paired with surface-enhanced Raman spectroscopy (SERS), can rapidly detect microRNA. However, widespread use of this approach is hindered by drawbacks associated with large and expensive benchtop Raman microscopes. MicroRNA-17 (miRNA-17) has emerged as a potential epigenetic indicator of preeclampsia, a condition that occurs during pregnancy. Biomarker detection using an SERS point-of-care device could enable prompt diagnosis and prevention as early as the first trimester...
January 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29303513/in-vitro-modeling-of-hepatocellular-carcinoma-molecular-subtypes-for-anti-cancer-drug-assessment
#18
Hadassa Hirschfield, C Billie Bian, Takaaki Higashi, Shigeki Nakagawa, Tizita Z Zeleke, Venugopalan D Nair, Bryan C Fuchs, Yujin Hoshida
Tractable experimental model that accounts for inter-tumor molecular heterogeneity is a key element of anti-cancer drug development. Hepatocellular carcinoma is known to exhibit highly heterogeneous molecular aberrations across the tumors, including somatic genetic and epigenetic alterations. Previous studies showed that molecular tumor subtypes determined by transcriptome, as a comprehensive functional readout, are reproducibly observed across global patient populations irrespective of geographic and etiological variations...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29302577/rna-binding-protein-as-an-emerging-therapeutic-target-for-cancer-prevention-and-treatment
#19
REVIEW
Suntaek Hong
After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis...
December 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29301935/-inhibition-of-histone-h3k27-demethylase-selectively-modulates-inflammatory-phenotypes-of-natural-killer-cells
#20
Adam Cribbs, Edward S Hookway, Graham Wells, Morten Lindow, Susanna Obad, Henrik Oerum, Rab K Prinjha, Nick Athanasou, Aneka Sowman, Martin Philpott, Henry Penn, Kalle Soderstrom, Marc Feldmann, Udo Oppermann
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically, but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets...
January 4, 2018: Journal of Biological Chemistry
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