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TET and EZH2

William M Skiles, Avery Kester, Jane H Pryor, Mark E Westhusin, Michael C Golding, Charles R Long
Embryo culture and assisted reproductive technologies have been associated with a disproportionately high number of epigenetic abnormalities in the resulting offspring. However, the mechanisms by which these techniques influence the epigenome remain poorly defined. In this study, we evaluated the capacity of oxygen concentration to influence the transcriptional control of a selection of key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen concentrations modulated the transcriptional regulation of the TET family of enzymes, as well as the de novo methyltransferase Dnmt3a...
June 2018: Gene Expression Patterns: GEP
Min Deng, Ruixin Zhang, Zhengxi He, Qinwei Qiu, Xihong Lu, Jiang Yin, Hao Liu, Xiaoting Jia, Zhimin He
DNA demethylases of the TET family function as tumor suppressors in various human cancers, but their pathogenic contributions and mechanisms of action in gastric carcinogenesis and progression remain unclear. Here, we report that TET is transcriptionally upregulated in gastric cancer, where it correlates with poor prognosis. Mechanistic investigations revealed that TET facilitated gastric carcinogenesis through a noncoding function of the 3'UTR, which interacted with miR-26. This interaction resulted in sequestration of miR-26 from its target EZH2, which released the suppression on EZH2, and thereby led to EZH2 overexpression in gastric cancer...
November 15, 2017: Cancer Research
Kolsoum Saeidi
Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by increased production of mature blood cells. Philadelphia chromosome-negative MPNs (Ph-MPNs) consist of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A number of stem cell derived mutations have been identified in the past 10 years. These findings showed that JAK2V617F, as a diagnostic marker involving JAK2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs. Somatic mutations in an endoplasmic reticulum chaperone, named calreticulin (CALR), is the second most common mutation in patients with ET and PMF after JAK2 V617F mutation...
February 2016: Critical Reviews in Oncology/hematology
Piotr Ciesielski, Paweł Jóźwiak, Anna Krześlak
Epigenetic modifications, including DNA methylation and histone modifications, are involved in regulation of gene expression, and alterations in these modifications are implicated in cancer onset and progression. The specific pattern of DNA methylation depends on the balance between methylation and demethylation processes. Recent studies have shown that TET proteins play a key role in DNA demethylation. TET proteins (TET1, TET2, TET3) are iron(II) and α-ketoglutarate dependent dioxygenases, and their enzymatic activity involves hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine and further to 5-formylcytosine and 5-carboxylcytosine...
December 16, 2015: Postȩpy Higieny i Medycyny Doświadczalnej
Lin Li, Xue-mei Sun
Novel recurrent somatic mutations have been identified in patients with myeloid malignancies including myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Mutations of tet methylcytosine dioxygenase 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase (IDH)1/2, enhancer of zeste homologue 2 (EZH2) and additional sex combs-like 1 (ASXL1) have been shown to play important roles in the regulation of epigenetic patterning, and may be used as molecular predictors for pathogenesis and clinical outcome for patients with myeloid malignancies...
December 2013: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Tomoya Muto, Goro Sashida, Motohiko Oshima, George R Wendt, Makiko Mochizuki-Kashio, Yasunobu Nagata, Masashi Sanada, Satoru Miyagi, Atsunori Saraya, Asuka Kamio, Genta Nagae, Chiaki Nakaseko, Koutaro Yokote, Kazuya Shimoda, Haruhiko Koseki, Yutaka Suzuki, Sumio Sugano, Hiroyuki Aburatani, Seishi Ogawa, Atsushi Iwama
Polycomb group (PcG) proteins are essential regulators of hematopoietic stem cells. Recent extensive mutation analyses of the myeloid malignancies have revealed that inactivating somatic mutations in PcG genes such as EZH2 and ASXL1 occur frequently in patients with myelodysplastic disorders including myelodysplastic syndromes (MDSs) and MDS/myeloproliferative neoplasm (MPN) overlap disorders (MDS/MPN). In our patient cohort, EZH2 mutations were also found and often coincided with tet methylcytosine dioxygenase 2 (TET2) mutations...
November 18, 2013: Journal of Experimental Medicine
Wendy N Jefferson, Dominique M Chevalier, Jazma Y Phelps, Amy M Cantor, Elizabeth Padilla-Banks, Retha R Newbold, Trevor K Archer, H Karimi Kinyamu, Carmen J Williams
Neonatal exposure to diethylstilbestrol (DES) causes permanent alterations in female reproductive tract gene expression, infertility, and uterine cancer in mice. To determine whether epigenetic mechanisms could explain these phenotypes, we first tested whether DES altered uterine expression of chromatin-modifying proteins. DES treatment significantly reduced expression of methylcytosine dioxygenase TET oncogene family, member 1 (TET1) on postnatal day 5; this decrease was correlated with a subtle decrease in DNA 5-hydroxymethylcytosine in adults...
October 2013: Molecular Endocrinology
A Tefferi, O Abdel-Wahab, F Cervantes, J D Crispino, G Finazzi, F Girodon, H Gisslinger, J Gotlib, J-J Kiladjian, R L Levine, J D Licht, A Mullally, O Odenike, A Pardanani, R T Silver, E Solary, T Mughal
Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN...
2011: Blood Cancer Journal
Maria A Hahn, Runxiang Qiu, Xiwei Wu, Arthur X Li, Heying Zhang, Jun Wang, Jonathan Jui, Seung-Gi Jin, Yong Jiang, Gerd P Pfeifer, Qiang Lu
DNA methylation in mammals is highly dynamic during germ cell and preimplantation development but is relatively static during the development of somatic tissues. 5-hydroxymethylcytosine (5hmC), created by oxidation of 5-methylcytosine (5mC) by Tet proteins and most abundant in the brain, is thought to be an intermediary toward 5mC demethylation. We investigated patterns of 5mC and 5hmC during neurogenesis in the embryonic mouse brain. 5hmC levels increase during neuronal differentiation. In neuronal cells, 5hmC is not enriched at enhancers but associates preferentially with gene bodies of activated neuronal function-related genes...
February 21, 2013: Cell Reports
Alan H Shih, Omar Abdel-Wahab, Jay P Patel, Ross L Levine
Recent genomic studies have identified novel recurrent somatic mutations in patients with myeloid malignancies, including myeloproliferative neoplasms (MPNs), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). In some cases these mutations occur in genes with known roles in regulating chromatin and/or methylation states in haematopoietic progenitors, and in other cases genetic and functional studies have elucidated a role for specific mutations in altering epigenetic patterning in myeloid malignancies...
September 2012: Nature Reviews. Cancer
Sandrine Sander, Lars Bullinger, Kay Klapproth, Katja Fiedler, Hans A Kestler, Thomas F E Barth, Peter Möller, Stephan Stilgenbauer, Jonathan R Pollack, Thomas Wirth
The MYC oncogene, which is commonly mutated/amplified in tumors, represents an important regulator of cell growth because of its ability to induce both proliferation and apoptosis. Recent evidence links MYC to altered miRNA expression, thereby suggesting that MYC-regulated miRNAs might contribute to tumorigenesis. To further analyze the impact of MYC-regulated miRNAs, we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system to control its expression. Microarray-based miRNA expression profiling revealed both known and novel MYC targets...
November 15, 2008: Blood
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