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Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers
- Source :
- Oncotarget
- Publication Year :
- 2011
- Publisher :
- Impact Journals LLC, 2011.
-
Abstract
- DNA methylation at the 5-position of cytosines (5 mC) represents an important epigenetic modification involved in tissue differentiation and is frequently altered in cancer. Recent evidence suggests that 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) in an enzymatic process involving members of the TET protein family. Such 5 hmC modifications are known to be prevalent in DNA of embryonic stem cells and in the brain, but the distribution of 5 hmC in the majority of embryonic and adult tissues has not been rigorously explored. Here, we describe an immunohistochemical detection method for 5 hmC and the application of this technique to study the distribution of 5 hmC in a large set of mouse and human tissues. We found that 5 hmC was abundant in the majority of embryonic and adult tissues. Additionally, the level of 5 hmC closely tracked with 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. Furthermore, 5 hmC levels were profoundly reduced in carcinoma of the prostate, breast and colon compared to normal tissues. Our findings suggest a distinct role for 5 hmC in tissue differentiation, and provide evidence for its large-scale loss in cancers.
- Subjects :
- Male
Pathology
medicine.medical_specialty
tissue stem/progenitor cells
Cellular differentiation
Down-Regulation
Breast Neoplasms
Gestational Age
Biology
Adenocarcinoma
03 medical and health sciences
chemistry.chemical_compound
Cytosine
Mice
0302 clinical medicine
medicine
cancer
Animals
Humans
Epigenetics
5-hydroxymethylcytosine
Progenitor cell
030304 developmental biology
5-Hydroxymethylcytosine
0303 health sciences
DNA methylation
Stem Cells
HEK 293 cells
Carcinoma, Ductal, Breast
Prostatic Neoplasms
Cell Differentiation
differentiation
Embryo, Mammalian
Embryonic stem cell
Research Papers
Immunohistochemistry
3. Good health
Cell biology
Mice, Inbred C57BL
HEK293 Cells
Oncology
chemistry
030220 oncology & carcinogenesis
Colonic Neoplasms
5-Methylcytosine
5hmC
Female
Stem cell
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 2
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....ccbd2ddaa36ba7fdbbe7ac180079d38b