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active DNA demethylation

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https://www.readbyqxmd.com/read/28318075/thymine-dna-glycosylase-modulates-dna-damage-response-and-gene-expression-by-base-excision-repair-dependent-and-independent-mechanisms
#1
Tomohumi Nakamura, Kouichi Murakami, Haruto Tada, Yoshihiko Uehara, Jumpei Nogami, Kazumitsu Maehara, Yasuyuki Ohkawa, Hisato Saitoh, Hideo Nishitani, Tetsuya Ono, Ryotaro Nishi, Masayuki Yokoi, Wataru Sakai, Kaoru Sugasawa
Thymine DNA glycosylase (TDG) is a base excision repair (BER) enzyme, which is implicated in correction of deamination-induced DNA mismatches, the DNA demethylation process and regulation of gene expression. Because of these pivotal roles associated, it is crucial to elucidate how the TDG functions are appropriately regulated in vivo. Here, we present evidence that the TDG protein undergoes degradation upon various types of DNA damage, including ultraviolet light (UV). The UV-induced degradation of TDG was dependent on proficiency in nucleotide excision repair and on CRL4(CDT)(2) -mediated ubiquitination that requires a physical interaction between TDG and DNA polymerase clamp PCNA...
March 20, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28294608/an-engineered-split-tet2-enzyme-for-inducible-epigenetic-remodeling
#2
Minjung Lee, Jia Li, Yi Liang, Guolin Ma, Jixiang Zhang, Lian He, Yuliang Liu, Qian Li, Minyong Li, Deqiang Sun, Yubin Zhou, Yun Huang
The Ten-eleven translocation (TET) family of 5-methylcytosine (5mC) dioxygenases catalyze the conversion of 5mC into 5-hydroxymethylcytosine (5hmC) and further oxidized species to promote active DNA demethylation. Here we engineered a split-TET2 enzyme to enable temporal control of 5mC oxidation and subsequent remodeling of epigenetic states in mammalian cells. We further demonstrate the use of this chemically-inducible system to dissect the correlation between DNA hydroxymethylation and chromatin accessibility in the mammalian genome...
March 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28277978/targeted-dna-demethylation-in-human-cells-by-fusion-of-a-plant-5-methylcytosine-dna-glycosylase-to-a-sequence-specific-dna-binding-domain
#3
Jara Teresa Parrilla-Doblas, Rafael R Ariza, Teresa Roldán-Arjona
DNA methylation is a crucial epigenetic mark associated to gene silencing, and its targeted removal is a major goal of epigenetic editing. In animal cells, DNA demethylation involves iterative 5mC oxidation by TET enzymes followed by replication-dependent dilution and/or replication-independent DNA repair of its oxidized derivatives. In contrast, plants use specific DNA glycosylases that directly excise 5mC and initiate its substitution for unmethylated C in a base excision repair process. In this work, we have fused the catalytic domain of Arabidopsis ROS1 5mC DNA glycosylase (ROS1_CD) to the DNA binding domain of yeast GAL4 (GBD)...
February 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28267381/dynamics-of-5-carboxylcytosine-during-hepatic-differentiation-potential-general-role-for-active-demethylation-by-dna-repair-in-lineage-specification
#4
Lara C Lewis, Peggy Cho Kiu Lo, Jeremy M Foster, Nan Dai, Ivan R Corrêa, Paulina M Durczak, Gary Duncan, Ashley Ramsawhook, Guruprasad Padur Aithal, Chris Denning, Nicholas R F Hannan, Alexey Ruzov
Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operative in this system; however, it is still unknown if TDG/BER-dependent demethylation is utilized during other types of cellular differentiation...
March 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28261894/sperm-dna-fragmentation-affects-epigenetic-feature-in-human-male-pronucleus
#5
H Rajabi, H Mohseni-Kouchesfehani, T Eslami-Arshaghi, M Salehi
To evaluate whether the sperm DNA fragmentation affects male pronucleus epigenetic factors, semen analysis was performed and DNA fragmentation was assessed by the method of sperm chromatin structure assay (SCSA). Human-mouse interspecies fertilisation was used to create human male pronucleus. Male pronucleus DNA methylation and H4K12 acetylation were evaluated by immunostaining. Results showed a significant positive correlation between the level of sperm DNA fragmentation and DNA methylation in male pronuclei...
March 6, 2017: Andrologia
https://www.readbyqxmd.com/read/28250235/methylation-dynamics-during-folliculogenesis-and-early-embryo-development-in-sheep
#6
Laura Masala, Giovanni Pietro Burrai, Emanuela Bellu, Federica Ariu, Luisa Bogliolo, Sergio Ledda, Daniela Bebbere
Genome-wide DNA methylation reprogramming occurs during mammalian gametogenesis and early embryogenesis. Post-fertilization demethylation of paternal and maternal genomes is considered to occur by an active and passive mechanism, respectively, in most mammals but sheep; in this species no loss of methylation was observed in either pronucleus. Post-fertilization reprogramming relies on methylating and de-methylating enzymes and co-factors that are stored during oocyte growth, concurrently with the re-methylation of the oocyte itself...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28246302/acquired-resistance-with-epigenetic-alterations-under-long-term-anti-angiogenic-therapy-for-hepatocellular-carcinoma
#7
Yoshiteru Ohata, Shu Shimada, Yoshimitsu Akiyama, Kaoru Mogushi, Keisuke Nakao, Satoshi Matsumura, Arihiro Aihara, Yusuke Mitsunori, Daisuke Ban, Takanori Ochiai, Atsushi Kudo, Shigeki Arii, Minoru Tanabe, Shinji Tanaka
Anti-angiogenic therapy is initially effective for several solid tumors including hepatocellular carcinoma (HCC); however, they finally relapse and progress, resulting in poor prognosis. We here established in vivo drug-tolerant subclones of human HCC cells by long-term treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor and serial transplantation in immunocompromised mice (total 12 months), and then compared them with the parental cells in molecular and biological features. Gene expression profiles elucidated a G-actin monomer binding protein thymosin β 4 (Tβ4) as one of the genes enriched in the resistant cancer cells relative to the initially sensitive ones...
February 28, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28242787/tet2-in-normal-and-malignant-hematopoiesis
#8
Robert L Bowman, Ross L Levine
The ten-eleven translocation (TET) family of enzymes were originally cloned from the translocation breakpoint of t(10;11) in infant acute myeloid leukemia (AML) with subsequent genomic analyses revealing somatic mutations and suppressed expression of TET family members across a range of malignancies, particularly enriched in hematological neoplasms. The TET family of enzymes is responsible for the hydroxylation of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), followed by active and passive mechanisms leading to DNA demethylation...
February 27, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28241740/hinokitiol-induces-dna-demethylation-via-dnmt1-and-uhrf1-inhibition-in-colon-cancer-cells
#9
Jung Seon Seo, Young Ha Choi, Ji Wook Moon, Hyeon Soo Kim, Sun-Hwa Park
BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co...
February 27, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28239297/up-regulation-of-crkl-by-microrna-335-methylation-is-associated-with-poor-prognosis-in-gastric-cancer
#10
Jia-Kui Zhang, Yong-Shuang Li, Chun-Dong Zhang, Dong-Qiu Dai
BACKGROUND: MicroRNAs have been suggested to play a vital role in regulating carcinogenesis, tumor progression and invasion. MiR-335 is involved in suppressing metastasis and invasion in various human cancers. However, the mechanisms responsible for the aberrant expression of miR-335 in gastric cancer (GC) remain unknown. METHODS: Expression of miR-335 in four GC cell lines and 231 GC tissues was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28225433/the-role-of-5-hydroxymethylcytosine-in-melanoma
#11
Feng-Juan Li, Li-Ming Li, Rui-Hua Zhang, Cui Xu, Pan Zhou, Jia Long, Gang Hu, Ming-Jun Jiang
Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation...
February 20, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28219743/significant-association-of-cyp19a-promoter-methylation-with-environmental-factors-and-gonadal-differentiation-in-olive-flounder-paralichthys-olivaceus
#12
Zhaofei Fan, Yuxia Zou, Shuang Jiao, Xungang Tan, Zhihao Wu, DongDong Liang, Peijun Zhang, Feng You
The sex ratio of olive flounder Paralichthys olivaceus is sensitive to temperature or exogenous hormone exposures in the period of gonadal differentiation. Among sex-related genes, cyp19a, encoding cytochrome P450 aromatase,exhibits significant sex-dimorphic expression pattern and plays an important role in fish gonadal differentiation and development. The present study investigated the expression levels and promoter methylation dynamics of cyp19a and its regulators (nr5a2 and nr0b1), and sex-steroid hormone levels during flounder gonadal differentiation under the treatments of high temperature and estradiol-17β (E2)...
February 17, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28215635/mechanical-stimulation-promote-the-osteogenic-differentiation-of-bone-marrow-stromal-cells-through-epigenetic-regulation-of-sonic-hedgehog
#13
Chuandong Wang, Shengzhou Shan, Chenglong Wang, Jing Wang, Jiao Li, Guoli Hu, Kerong Dai, Qingfeng Li, Xiaoling Zhang
Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of Sonic hedgehog (Shh) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28204824/dna-methylation-mediated-caspase-8-downregulation-is-associated-with-anti-apoptotic-activity-and-human-malignant-glioma-grade
#14
Yueqiu Teng, Yu-Cui Dong, Zhaoyu Liu, Yan Zou, Hui Xie, Yu Zhao, Jun Su, Fenglin Cao, Hua Jin, Huan Ren
The methylation-mediated silencing of tumor suppressors, including key apoptosis-related genes plays an important role in the pathogenesis and therapeutic resistance in human cancer. In this study, we aimed to elucidate the role and mechanisms of resistance to apoptosis with caspase-8 gene downregulation in human malignant glioma. Reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP) were used to examine caspase-8 expressoin at the mRNA level and gene methylation status in normal brain tissue, glioma tissue and cancer cell lines...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28198363/gut-memories-do-not-fade-epigenetic-regulation-of-lasting-gut-homing-receptor-expression-in-cd4-memory-t-cells
#15
B A Szilagyi, J Triebus, C Kressler, M de Almeida, S Tierling, P Durek, M Mardahl, A Szilagyi, S Floess, J Huehn, U Syrbe, J Walter, J K Polansky, A Hamann
The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28192139/vitamin-c-down-regulate-apo-a-expression-via-tet2-dependent-dna-demethylation-in-hepg2-cells
#16
Kai Qu, Xiao-Feng Ma, Guo-Hua Li, Hai Zhang, Ya-Mi Liu, Kai Zhang, Jun-Fa Zeng, Jian-Jun Lei, Dang-Heng Wei, Zuo Wang
Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice...
February 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28188826/convenient-expression-purification-and-quantitative-liquid-chromatography-tandem-mass-spectrometry-based-analysis-of-tet2-5-methylcytosine-demethylase
#17
Mohit Jaiswal, Subhradeep Bhar, Harika Vemula, Swami Prakash, V K Chaithanya Ponnaluri, William G Gutheil, Mridul Mukherji
5-Methylcytosine within CpG islands in DNA plays a crucial role in epigenetic transcriptional regulation during metazoan development. Recently, it has been established that the Ten-Eleven Translocation (TET) family, Fe(II)- and 2-oxoglutarate (2OG/αKG)-dependent oxygenases initiate 5-methylcytosine demethylation by iterative oxidation reactions. Mutations in the TET2 gene are frequently detected in patients with myeloid malignancies. Here, we describe the cloning of untagged human TET2 demethylase using Gateway technology and its efficient expression in E...
February 8, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28186961/combination-epigenetic-therapy-in-metastatic-colorectal-cancer-mcrc-with-subcutaneous-5-azacitidine-and-entinostat-a-phase-2-consortium-stand-up-2-cancer-study
#18
Nilofer S Azad, Anthony El-Khoueiry, Jun Yin, Ann L Oberg, Patrick Flynn, Douglas Adkins, Anup Sharma, Daniel J Weisenberger, Thomas Brown, Prakriti Medvari, Peter A Jones, Hariharan Easwaran, Ihab Kamel, Nathan Bahary, George Kim, Joel Picus, Henry C Pitot, Charles Erlichman, Ross Donehower, Hui Shen, Peter W Laird, Richard Piekarz, Stephen Baylin, Nita Ahuja
PURPOSE: Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. EXPERIMENTAL DESIGN: We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 75 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10...
February 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28169463/relationship-between-epigenetic-regulation-dietary-habits-and-the-developmental-origins-of-health-and-disease-theory
#19
REVIEW
Kazuki Mochizuki, Natsuyo Hariya, Kazue Honma, Toshinao Goda
Environmental stressors during developmental stages are hypothesized to increase the risk of developing metabolic diseases such as obesity, type 2 diabetes, hypertension, and psychiatric diseases during later life. This theory is known as the Developmental Origins of Health and Disease (DOHaD). Recent studies suggest that accumulation of environmental stress, including during developmental stages, is internalized as acquired information designated as "epigenetic memory." This epigenetic memory is generally indicated as DNA methylation and histone modifications in the chromatin...
February 7, 2017: Congenital Anomalies
https://www.readbyqxmd.com/read/28169339/dna-methylation-governs-the-dynamic-regulation-of-inflammation-by-apoptotic-cells-during-efferocytosis
#20
Clare A Notley, Christine K Jordan, Jenny L McGovern, Mark A Brown, Michael R Ehrenstein
Efficient clearance of apoptotic cells (AC) is pivotal in preventing autoimmunity and is a potent immunosuppressive stimulus. However, activation of cells prior to apoptosis abolishes their immunoregulatory properties. Here we show using the antigen-induced model of arthritis that the degree of DNA methylation within AC confers their immunomodulatory plasticity. DNA isolated from resting and activated AC mimicked their respective immune effects. Demethylation of DNA abrogated the protective effect of AC whereas remethylation of AC DNA reversed the effects of activation and restored the ability to inhibit inflammation...
February 7, 2017: Scientific Reports
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