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Homocysteine is an intermediary metabolite produced from the hydrolysis of S\u2010adenosylhomocysteine (SAH), which is a by\u2010product of methylation reactions involving the methyl\u2010donor S\u2010adenosylmethionine (SAM). Here, we have measured SAM, SAH, DNA and histone methylation status in an inducible mouse model of CBS deficiency to test the hypothesis that homocysteine\u2010related phenotypes are caused by inhibition of methylation due to elevated SAH and reduced SAM\/SAH ratio. We found that mice lacking CBS have elevated cellular SAH and reduced SAM\/SAH ratios in both liver and kidney, but this was not associated with alterations in the level of 5\u2010methylcytosine or various histone modifications. Using methylated DNA immunoprecipitation in combination with microarray, we found that of the 241 most differentially methylated promoter probes, 89 % were actually hypermethylated in CBS deficient mice. In addition, we did not find that changes in DNA methylation correlated well with changes in RNA expression in the livers of induced and uninduced CBS mice. Our data indicates that reduction in the SAM\/SAH ratio, due to loss of CBS activity, does not result in overall hypomethylation of either DNA or histones.<\/jats:p>","DOI":"10.1007\/s10545-016-9958-5","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T09:29:44Z","timestamp":1469093384000},"page":"113-120","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Lack of global epigenetic methylation defects in CBS deficient mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Hyung\u2010Ok","family":"Lee","sequence":"first","affiliation":[{"name":"Cancer Biology Program Fox Chase Cancer Center 333 Cottman Avenue Philadelphia PA 19111 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Biology Program Fox Chase Cancer Center 333 Cottman Avenue Philadelphia PA 19111 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