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5-hydroxymethylcytosine in Differentiation & Cancer

Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers
This study from collaborators at Johns Hopkins University details a new immunohistochemistry (IHC) method that was used to study the global distribution of 5-hydroxymethylcytosine (5-hmC) in a large set of mouse and human tissues. The paper shows that 5-hmC was abundant in the majority of embryonic and adult tissues, and that the level of 5-hmC closely tracked the differentiation state of cells in hierarchically organized tissues. The highest 5-hmC levels were observed in terminally differentiated cells, while less differentiated tissue stem/progenitor cell compartments had very low 5-hmC levels. In addition, 5-hmC levels were greatly reduced in prostate, breast and colon carcinoma compared to normal tissues. The findings suggest a role for 5-hmC in tissue differentiation, as opposed to its relative absence in cancers.
Haffner et al. (2011) Oncotarget 2(8):627-637. Abstract.
   Active Motif products cited in this paper:
         5-Hydroxymethylcytosine (5-hmC) polyclonal antibody
   Active Motif products relevant to this paper:
         5-Hydroxymethylcytosine (5-hmC) monoclonal & polyclonal antibodies
         5-Methylcytosine (5-mC) monoclonal antibody
         Hydroxymethyl Collector™
         hMeDIP Kit
         Methylated DNA Standard Kit
 

Novel Forms of DNA Methylation Studied In Vivo

Role of 5hmC/5fC/5caC in DNA demethylation during development
DNA methylation is an important part of the mechanisms by which DNA accessibility and chromatin structure are regulated. Until the discovery of 5-hydroxymethylcytosine (5-hmC) methylation, the term “DNA methylation” referred only to 5-methylcytosine methylation (5-mC). Now, two more forms of cytosine methylation are in the news, 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). These are enzymatic descendants of 5-hydroxymethylcytosine, as they result from the conversion of 5-hmC by the same family of enzymes that catalyze 5-hmC synthesis, the TET cytosine oxygenases. Researchers at the University of North Carolina at Chapel Hill have found that increased levels of 5-fC and 5-caC can be detected in the mouse male pronucleus following fertilization, which then are gradually diluted by subsequent rounds of DNA replication during cell division.
Inoue et al. (2011) Cell Research 21(12):1670-1676. Abstract.
   Active Motif products cited in this paper:
         5-Formylcytosine (5-fC) polyclonal antibody
         5-Carboxylcytosine (5-caC) polyclonal antibody
         5-Hydroxymethylcytosine (5-hmC) polyclonal antibody
 

Methylation of the N3 of Cytosine (3-methylcytosine)

A novel connection between DNA methylation and cancer identified
Methylation of the C5 of cytosine (5-methylcytosine) is an epigenetic mark regulating genome function, but methylation of the N3 position is potentially mutagenic. Multiple mechanisms exist to repair this type of DNA lesion, and a recent study at Harvard University sheds light on the mechanism of one such repair protein, ALKBH3. ALKBH3 was found to be associated with a protein complex (ASCC) previously implicated in transcriptional activation. One subunit of the ASCC complex, ASCC3, encodes a DNA helicase that creates a region of single-stranded DNA that is required by ALKBH3 to facilitate repair of the methyl adduct. Loss of the ALKBH3 repair activity was found to reduce proliferation of several tumor cell lines in culture, and resulted in impaired tumor formation in mouse xenograft models. It is possible that ALKBH3 or ASCC3 could be targeted for therapeutic intervention in cancer.
Dango et al. (2011) Molecular Cell 44(3):373-384. Abstract.
   Active Motif products cited in this paper:
         3-Methylcytosine (3-mC) polyclonal antibody (Serum)
   Active Motif products relevant to this paper:
         3-Methylcytosine (3-mC) polyclonal antibody (IgG)
         Histone H2AX phospho Ser139 polyclonal antibody

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