Structure and Function of TET Enzymes

Yin, Xiaoxue; Hu, Lulu; Xu, Yanhui

doi:10.1007/978-3-031-11454-0_10

Cited by 8 publications

(6 citation statements)

References 229 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During male germ cell differentiation, DNA methylation is controled by the activity of the DNA methyltransferases (DNMTs), i.e., DNMT3A, DNMT3B, and their cofactor DNMT3L for the de novo methylation [ 17 , 18 ], while DNA demethylases (TET enzymes) is involved in demethylation to maintain normal gene expression [ 19 ]. In addition, DNMT1 is responsible for methylation maintenance during the different phases of spermatogenesis in the adulthood period [ 20 – 22 ].…”

Section: The Epigenome Of Bovine Spermmentioning

confidence: 99%

Harnessing male germline epigenomics for the genetic improvement in cattle

Wang

Feng

et al. 2023

J Animal Sci Biotechnol

View full text Add to dashboard Cite

Sperm is essential for successful artificial insemination in dairy cattle, and its quality can be influenced by both epigenetic modification and epigenetic inheritance. The bovine germline differentiation is characterized by epigenetic reprogramming, while intergenerational and transgenerational epigenetic inheritance can influence the offspring’s development through the transmission of epigenetic features to the offspring via the germline. Therefore, the selection of bulls with superior sperm quality for the production and fertility traits requires a better understanding of the epigenetic mechanism and more accurate identifications of epigenetic biomarkers. We have comprehensively reviewed the current progress in the studies of bovine sperm epigenome in terms of both resources and biological discovery in order to provide perspectives on how to harness this valuable information for genetic improvement in the cattle breeding industry.

show abstract

Section: The Epigenome Of Bovine Spermmentioning

confidence: 99%

Harnessing male germline epigenomics for the genetic improvement in cattle

Wang

Feng

et al. 2023

J Animal Sci Biotechnol

View full text Add to dashboard Cite

show abstract

“…In the current study, patients harboring the H1778R variant in TET2 was found to have a low TET2 protein expression and 5-hmC immunostaining on IHC, and this variant was further subjected to molecular dynamics simulation studies. The less conserved LCI has been predicted to have regulatory roles in the TET gene family through interaction with DNA, [ 53 ] protein–protein interactions, or probable post-translational modifications [ 39 , 54 ]. The crystal structure of minimally active TET2-CD harbors a Glycine-Serine linker (GS linker) in place of the LCI, proximal to the major groove of DNA.…”

Section: Discussionmentioning

confidence: 99%

Alterations of the expression of TET2 and DNA 5-hmC predict poor prognosis in Myelodysplastic Neoplasms

Seethy,

Pethusamy,

Kushwaha

et al. 2023

BMC Cancer

View full text Add to dashboard Cite

Background Myelodysplastic Neoplasms (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis and progression to acute myeloid leukemia, myelodysplasia-related (AML-MR). A major mechanism of pathogenesis of MDS is the aberration of the epigenetic landscape of the hematopoietic stem cells and/or progenitor cells, especially DNA cytosine methylation, and demethylation. Data on TET2, the predominant DNA demethylator of the hematopoietic system, is limited, particularly in the MDS patients from India, whose biology may differ since these patients present at a relatively younger age. We studied the expression and the variants of TET2 in Indian MDS and AML-MR patients and their effects on 5-hydroxymethyl cytosine (5-hmC, a product of TET2 catalysis) and on the prognosis of MDS patients. Results Of the 42 MDS patients, cytogenetics was available for 31 sub-categorized according to the Revised International Prognostic Scoring System (IPSS-R). Their age resembled that of the previous studies from India. Bone marrow nucleated cells (BMNCs) were also obtained from 13 patients with AML-MR, 26 patients with de-novo AML, and 11 subjects with morphologically normal bone marrow. The patients had a significantly lower TET2 expression which was more pronounced in AML-MR and the IPSS-R higher-risk MDS categories. The 5-hmC levels in higher-risk MDS and AML-MR correlated with TET2 expression, suggesting a possible mechanistic role in the loss of TET2 expression. The findings on TET2 and 5-hmC were also confirmed at the tissue level using immunohistochemistry. Pathogenic variants of TET2 were found in 7 of 24 patient samples (29%), spanning across the IPSS-R prognostic categories. One of the variants – H1778R – was found to affect local and global TET2 structure when studied using structural predictions and molecular dynamics simulations. Thus, it is plausible that some pathogenic variants in TET2 can compromise the structure of TET2 and hence in the formation of 5-hmC. Conclusions IPSS-R higher-risk MDS categories and AML-MR showed a reduction in TET2 expression, which was not apparent in lower-risk MDS. DNA 5-hmC levels followed a similar pattern. Overall, a decreased TET2 expression and a low DNA 5-hmC level are predictors of advanced disease and adverse outcome in MDS in the population studied, i.e., MDS patients from India.

show abstract

“…The hydroxylase activity catalyzed by Ten Eleven Translocation 1 (TET1) converts methylcytosine into hydroxymethylcytosine [35]. The same enzyme also catalyzes further steps toward demethylation and the consequent modulation of gene expression [36]. It has been demonstrated that TET activity is strictly AsA-dependent [37], opening new and unexpected perspectives into our understanding of AsA biological function.…”

Section: Integration Of Different Signals By 2-odds: Hif Prolyl Hydro...mentioning

confidence: 99%

The Function of Ascorbic Acid through Occam’s Razor: What We Know, What We Presume and What We Hope For

Tullio¹

2024

Ascorbic Acid - Biochemistry and Functions

View full text Add to dashboard Cite

After being identified as the anti-scurvy factor vitamin C, ascorbic acid (AsA) became the subject of an astonishing amount of research. Many studies confirmed that AsA is essential to plants and animals, however, the molecular mechanisms by which AsA exerts its action are only in part understood. Much attention has been given to the so-called antioxidant function of AsA, but the concept of antioxidant is in itself rather vague and, at least in some studies, proper quantitative approaches to assess the actual relevance of AsA as an antioxidant are lacking. On the other hand, in the last few decades more and more research focused on the specific function of AsA as a regulatory co-factor of 2-oxoglutarate-dependent dioxygenases, a large class of enzymes catalyzing an array of different and apparently unrelated reactions, all sharing a complex mechanism based on the integration of relevant pieces of molecular information. The present contribution aims to critically discuss available evidence in support of current hypotheses on AsA function.

show abstract

Structure and Function of TET Enzymes

Cited by 8 publications

References 229 publications

Harnessing male germline epigenomics for the genetic improvement in cattle

Harnessing male germline epigenomics for the genetic improvement in cattle

Alterations of the expression of TET2 and DNA 5-hmC predict poor prognosis in Myelodysplastic Neoplasms

The Function of Ascorbic Acid through Occam’s Razor: What We Know, What We Presume and What We Hope For

Contact Info

Product

Resources

About