DNA methylation in genomic imprinting, development, and disease

Paulsen, Martina; Ferguson-Smith, Anne C.

doi:10.1002/path.890

Cited by 245 publications

(156 citation statements)

References 127 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…Because the GABA A -␤3 gene has been localized to a region of chromosome 15 that is associated with genetic imprinting, 27,28 hypermethylation of the CpG islands present on the upstream promoter could explain this finding. 29 However, we could not detect such hypermethylation using computer-generated primers. Thus, additional studies are required to elucidate the mechanism(s) involved.…”

Section: Discussionmentioning

confidence: 93%

Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma

et al. 2007

View full text Add to dashboard Cite

To determine whether hepatocyte membrane potential differences (PDs) are depolarized in human HCC and whether depolarization is associated with changes in GABA A receptor expression, hepatocyte PDs and ␥-aminobutyric acid (GABA) A receptor messenger RNA (mRNA) and protein expression were documented in HCC tissues via microelectrode impalement, real-time reverse-transcriptase polymerase chain reaction, and Western blot analysis, respectively. HCC tissues were significantly depolarized (؊19.8 ؎ 1.3 versus ؊25. In recent in vitro studies, we demonstrated that restoration of depolarized malignant hepatocyte cell membrane potential differences (PDs) toward those documented in nonmalignant hepatocytes results in a loss of malignant features, including decreased proliferative activity, absence of colony formation in soft agar, and normalization of phenotypic appearance. 2 Whether HCC tissues are depolarized relative to adjacent nontumor tissues and the mechanisms whereby such depolarization might exist have yet to be reported.

show abstract

Section: Discussionmentioning

confidence: 93%

Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In addition, the stabilization of gene silencing was due to increased methylation. [16][17][18]23,26,27 Thus, the elimination and methylation of integrated cDNA appeared to occur through different mechanisms. It is not likely that cDNA elimination is induced after methylation.…”

Section: Discussionmentioning

confidence: 99%

“…Epigenetic events such as DNA methylation [16][17][18] and histone deacetylation 19,20 result in gene silencing. Therefore, we examined whether histone acetylation is associated with decreased CD95 expression using TSA 37 (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18] We therefore examined whether this could account for the decreased CD95 expression in clones g7 and j5. g7 and j5 cells were incubated for 48-72 hr with different concentrations of an irreversible inhibitor of DNA methylation, 5-aza-2 0 -dC.…”

Section: Recovery Of Cd95 Expression By the Inhibition Of Dna Methylamentioning

confidence: 99%

“…Moreover, epigenetic phenomena, which consist of DNA methylation [16][17][18] and histone deacetylation, 19,20 result in the silencing of genes with no change in their DNA coding sequence. The methylation of cytosines in the CpG dinucleotide represses gene transcription leading to gene silencing.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Frequency and resistance of CD95 (Fas/Apo‐1) gene‐transfected tumor cells to CD95‐mediated apoptosis by the elimination and methylation of integrated DNA

Shimizu

Yoshimoto

Sato

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

It is important for more effective gene therapies to clarify the mechanisms by which cDNA integrated into cells can maintain or lose its function in vivo. We evaluated genetic and epigenetic events leading to alternation of the introduced CD95 (Fas/Apo-1) gene as a model of gene therapy. Solid tumors formed by CD95 cDNA-transfected hepatoma cells (F6b) were almost completely cured by a single treatment of anti-CD95 monoclonal antibody (mAb) but recurred in gld/gld lpr/lpr mice after initial complete response. Recurred tumors were resistant to repeated mAb treatment. The ratio of resistant cells in tumors was estimated as 4.2 cells per 10 6 cells. The CD95-resistant tumor contained CD95-vanished and CD95-decreased cells. CD95-vanished cells were due to the deletion of CD95cDNA. However, CD95-decreased cells retained CD95cDNA, which was highly methylated when determined with methylation-dependent enzymes and a demethylation reagent, indicating that DNA methylation was responsible for the reduced CD95 expression and resistance to mAb. CD95-decreased cells reduced the CD95 expression further but did not delete cDNA after a second in vivo treatment with anti-CD95 mAb, suggesting that the elimination of cDNA is not induced after its methylation and that cells containing methylated genes became more resistant by further methylation. Thus, the elimination and methylation of integrated cDNA appear to occur through different mechanisms. Our study of resistant tumor cells, which arose by both mutational and epigenetic modifications of the introduced CD95 plasmid, provides important and fundamental information about the fate of introduced cDNA, augmenting the efficiency of gene therapy. ' 2006 Wiley-Liss, Inc.Key words: CD95/Fas/Apo-1; apoptosis; epigenetics; mutation frequency; cDNA methylation; cDNA deletion CD95/Fas/Apo-1 is a type I membrane protein that plays a crucial role in the regulation of cellular homeostasis. [1][2][3][4] In the immune system, CD95 and the CD95 ligand (CD95L) are involved in the induction of apoptosis by T-cell-mediated cytotoxicity 5,6 and the development of T cells, 7 thus, CD95 is a good target for tumor cell gene therapy. 8,9 However, a study of CD95-mediated tumor therapy in the syngeneic system has been hampered by lethal liver damage induced by antibodies to CD95 in wild type mice. 10 Most mice died within 6 hr after an intraperitoneal (i.p.) injection of 100 lg anti-CD95 monoclonal antibody (mAb). Thus, whether murine CD95-mediated apoptosis is indeed involved in the death pathway of murine tumor cells remains to be addressed. On the other hand, mutant mice, lpr and gld, carry a loss-of-function in CD95 and CD95L, respectively. 11 We have overcome this problem by using double-mutant mice which carry both gld and lpr mutations in a homogenous state and therefore express neither functional CD95L nor CD95. 12 These mice are completely resistant to the administration of anti-CD95 mAb. Moreover, they have the advantage of avoiding the possible influences of endogenous CD95L on CD95 1 tumor c...

show abstract

Growth Factor Receptors and Signal Transduction Regulating the Proliferation and Differentiation of Melanocytes

Halaban¹,

Moellmann²

2006

The Pigmentary System

View full text Add to dashboard Cite

DNA methylation in genomic imprinting, development, and disease

Cited by 245 publications

References 127 publications

Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma

Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma

Frequency and resistance of CD95 (Fas/Apo‐1) gene‐transfected tumor cells to CD95‐mediated apoptosis by the elimination and methylation of integrated DNA

Growth Factor Receptors and Signal Transduction Regulating the Proliferation and Differentiation of Melanocytes

Contact Info

Product

Resources

About