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5-hydroxymethylcytosine

 
5-methylcytosine (5mC) can be oxidized enzymatically by the TET family of proteins to form 5-hydroxymethylcytosine (5hmC). This process occurs genome-wide in the sperm-derived paternal genome shortly after fertilization (Iqbal et al., 2011). One popular model proposes that 5hmC is a transient intermediate in DNA demethylation. However, this issue is still unresolved and needs to be investigated further. We found that 5hmC is strongly depleted in many types of human cancer and could be developed as a biomarker for malignant disease (Jin et al., 2011). One of our hypotheses is that defects in 5mC oxidation are responsible for altered DNA methylation patterns in tumors (and possibly other diseases). We have established and used methodology for precise quantification and genome-wide mapping of 5mC and 5hmC. Our goal is to determine the levels and the genomic distribution of 5hmC in normal human tissues and in malignant tumors. We will focus on several tumor types, including solid tumors and hematological malignancies, which are often characterized by mutations in one of the TET genes, TET2, a methylcytosine oxidase. We work on basic mechanistic studies of TET and TET-associated proteins (for example, CXXC domain containing proteins), their aberrations in cancer and on their functional roles in control of CpG island methylation and cell differentiation.
 
Iqbal, K., Jin, S.-G., Pfeifer, G.P., and Szabó, P.E. (2011) Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine  Proc. Natl. Acad. Sci. USA 108, 3642-3647.
 
Jin, S.-G., Jiang, Y., Qiu, R., Rauch, T.A., Wang, Y., Schackert, G., Krex, D., Lu, Q., and Pfeifer, G.P. (2011) 5-hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations, Cancer Res. 71, 7360-7365.
 
Hahn, M.A., Qiu, R., Wu, X., Li, A.X., Wang, J., Zhang, H., Jui, J., Jin, S.G., Jiang, Y., Pfeifer, G.P.,* and Lu, Q.* (2013) Dynamics of 5-hydroxymethylcytosine and chromatin marks in mammalian neurogenesis, Cell Reports 3, 291-300.
 
Pfeifer, G.P., Kadam, S., and Jin, S.-G. (2013) 5-hydroxymethylcytosine and its potential roles in development and cancer, Epigenetics Chromatin 6(1):10.
 

 
 

5-hydroxymethylcytosine

5-hydroxymethylcytosine

 
5-methylcytosine (5mC) can be oxidized enzymatically by the TET family of proteins to form 5-hydroxymethylcytosine (5hmC). This process occurs genome-wide in the sperm-derived paternal genome shortly after fertilization (Iqbal et al., 2011). One popular model proposes that 5hmC is a transient intermediate in DNA demethylation. However, this issue is still unresolved and needs to be investigated further. We found that 5hmC is strongly depleted in many types of human cancer and could be developed as a biomarker for malignant disease (Jin et al., 2011). One of our hypotheses is that defects in 5mC oxidation are responsible for altered DNA methylation patterns in tumors (and possibly other diseases). We have established and used methodology for precise quantification and genome-wide mapping of 5mC and 5hmC. Our goal is to determine the levels and the genomic distribution of 5hmC in normal human tissues and in malignant tumors. We will focus on several tumor types, including solid tumors and hematological malignancies, which are often characterized by mutations in one of the TET genes, TET2, a methylcytosine oxidase. We work on basic mechanistic studies of TET and TET-associated proteins (for example, CXXC domain containing proteins), their aberrations in cancer and on their functional roles in control of CpG island methylation and cell differentiation.
 
Iqbal, K., Jin, S.-G., Pfeifer, G.P., and Szabó, P.E. (2011) Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine  Proc. Natl. Acad. Sci. USA 108, 3642-3647.
 
Jin, S.-G., Jiang, Y., Qiu, R., Rauch, T.A., Wang, Y., Schackert, G., Krex, D., Lu, Q., and Pfeifer, G.P. (2011) 5-hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations, Cancer Res. 71, 7360-7365.
 
Hahn, M.A., Qiu, R., Wu, X., Li, A.X., Wang, J., Zhang, H., Jui, J., Jin, S.G., Jiang, Y., Pfeifer, G.P.,* and Lu, Q.* (2013) Dynamics of 5-hydroxymethylcytosine and chromatin marks in mammalian neurogenesis, Cell Reports 3, 291-300.
 
Pfeifer, G.P., Kadam, S., and Jin, S.-G. (2013) 5-hydroxymethylcytosine and its potential roles in development and cancer, Epigenetics Chromatin 6(1):10.
 

 
 
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