Browsing by Subject "5-hmC"

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    Regulation of DNA methylation levels in the process of oral mucosal regeneration of oral ulcer model.
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Akiyama, Naotaro; Fukuda, Tomomi Yamamoto; Yoshikawa, Mamoru; Kojima, Hiromi
    DNA methylation is an important epigenetic mechanism for cellular maintenance. However, the methylation pattern and the key molecule regulated epigenetically in oral mucosal regeneration is unclear. In this study, we generated a rat oral ulcer model and investigated the cell proliferative activities and DNA methylation patterns immunohistochemically. We also performed immunohistochemical analysis of a regulator of epithelial stem/progenitor cell differentiation in the rat model. We demonstrated immunohistochemistry using antibodies for the molecules as follows: Ki-67, a marker of cellular proliferation; 5-methylcytosine (5-mC), a marker of DNA methylation; 5-hydroxymethylcytosine (5-hmC), a marker of DNA demethylation; Dnmt1, a maintenance DNA methyltransferase; Dnmt3a and Dnmt3b, de novo DNA methyltransferases; and Wnt5a, a regulator of stem/progenitor cell differentiation. In this model, re-epithelialization was completed at Day 4 after ulceration. Regenerating mucosal hypertrophy reached a peak at Day 5 and appeared normal at Day 14. Ki-67-positive cells increased at Day 2 and returned to normal at Day 6 after ulceration. The ratio of the expression level of 5-mC to 5-hmC declined at Day 5 and returned to normal at Day 6. The expression level of Dnmt1 had not changed compared to the normal control at every time point. On the other hand, the expression levels of Dnmt3a and Dnmt3b had decreased significantly at Day 5 and returned to normal at Day 6. Moreover, Wnt5a-positive cells increased at Day 5. In conclusion, oral mucosal regeneration was strictly regulated by DNA methylation. Moreover, Wnt5a might play a critical role in oral mucosal regeneration.
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    The role of TET family proteins and 5-hydroxymethylcytosine in human tumors
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Wu, Yi-Chen; Ling, Zhi-Qiang
    Tumorigenesis correlates with hypermethylation of tumor suppressors and hypomethylation of oncogenes. DNA methyltransferases (DNMTs) catalyze DNA methylation, and mutations and aberrant expression in DNMT genes are found in multiple human tumors. The discovery of the DNA demethylation function of TET proteins has opened up new avenues for the study of DNA methylation regulation. TET proteins regulate the DNA demethylation pathway through oxidizing 5-mC into 5-hmC, 5-fC, and 5-aC. TET genes have been reported to be frequently mutated in hematopoietic malignancies and are associated with the malignant transformation of cells. Loss-of-function mutations in TET genes have not been reported in human solid tumors. However, 5-hmC has been found to be reduced in various solid tumors, indicating that TET genes may contribute to cellular transformation via regulation of DNA demethylation. As a new epigenetic modification, 5-hmC may be a useful biomarker for the diagnosis of cancers. To better understand the roles of TET and 5-hmC in tumors, the biological functions of TET and 5-hmC should be studied further.