DNA methylation and hydroxymethylation in hematologic differentiation and transformation

Abstract

Maintenance of the balance of DNA methylation and demethylation is fundamental for normal cellular development and function. Members of the Ten-Eleven-Translocation (TET) family proteins are Fe(II)- and 2-oxoglutarate-dependent dioxygenases that catalyze sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and subsequent oxidized derivatives in DNA. In addition to their roles as intermediates in DNA demethylation, these oxidized methylcytosines are novel epigenetic modifications of DNA. DNA methylation and hydroxymethylation profiles are markedly disrupted in a wide range of cancers but how these changes are related to the pathogenesis of cancers is still ambiguous. In this review, we discuss the current understanding of TET protein functions in normal and malignant hematopoietic development and the ongoing questions to be resolved.

Prostate Cancer Patients–Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

“…These three oxidized methylcytosines point out the occurrence of both passive and active DNA demethylation and also serve as stable epigenetic marks34. Enzymatic mechanisms for removal of DNA methylation may release repaired products into the bloodstream and consequently they can appear in the urine.…”

TET proteins in natural and induced differentiation

“…Loss of Tet gene expression or altered TET enzymatic activity is associated with many human cancers [3]. In particular, mutations altering the enzymatic activity of TET2 have been associated with myelodysplastic syndromes [11] and characterized by the expansion of immature myeloid cells.…”

“…DNA methylation is controlled by the enzymes of the DNA methyltransferase family (DNMT) and the distribution of 5-methylcytosine (5mC) in the genome varies between lineages during development and in cancer [2,3]. A new mechanism to actively influence DNA methylation patterns was identified by the discovery of the Ten-eleven-translocation (TET) proteins [4,5].…”

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

“…These three oxidized methylcytosines may indicate the occurrence of both passive and active DNA demethylation and also serve as stable epigenetic marks (Ko et al, 2015). 5hmC is mainly involved in the up-regulation of gene expression, affecting cellular processes such as differentiation, somatic cell reprogramming, and embryonic development (Gao et al, 2013;Ito et al, 2010;Koh et al, 2011).…”