Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver

Farah Esfandiari, Ralph Green, Rebecca F. Cotterman, Igor P. Pogribny, S. Jill James, Joshua W. Miller

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

MeCP2 is a member of a family of proteins [methyl-(cytosine-guanine)CpG-binding proteins] that bind specifically to methylated DNA and induce chromatin remodeling and gene silencing. Dietary deficiency of folate, choline and methionine causes decreased tissue S-adenosylmethionine concentrations (methyl deficiency), global DNA hypomethylation, hepatic steatosis, cirrhosis and ultimately hepatic tumorigenesis in rodents. We investigated the effects of this diet on expression of MeCP2 during preneoplastic transformation of liver tissue. After 9 weeks, MeCP2 mRNA level was slightly higher in methyl-deficient rats compared with replete controls, while after 36 weeks, a difference in MeCP2 mRNA level was no longer observed. In contrast, MeCP2 protein level was reduced almost 2-fold in the deficient rats compared with replete controls at both 9 and 36 weeks. Conversely, a second methyl-CpG-binding protein, MBD2, showed increased levels of both message and protein at the two time points. Low MeCP2 protein in the deficient rats was associated with a low level of the co-repressor protein, Sin3a, at 36 weeks. Moreover, a known gene target of MeCP2, the tumor suppressor gene metallothionein-I, was over-expressed in the deficient rat livers at both 9 and 36 weeks, suggesting that reduction in MeCP2 may have functional consequences. Methyl deficiency also caused an increase in the ratio of long to short variants of MeCP2 transcripts. This finding suggests that reduced MeCP2 protein level is the result of a reduced rate of translation. Reduction of MeCP2 protein expression may influence the initiation and/or progression of hepatic cancer induced by methyl deficiency and may provide a useful marker of pre-neoplastic change.

Original languageEnglish (US)
Pages (from-to)1935-1940
Number of pages6
JournalCarcinogenesis
Volume24
Issue number12
DOIs
StatePublished - Dec 2003

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Methyl-CpG-Binding Protein 2
Carrier Proteins
Liver
Choline Deficiency
S-Adenosylmethionine
Co-Repressor Proteins
Messenger RNA
Chromatin Assembly and Disassembly
Metallothionein
Cytosine
DNA
Guanine
Gene Silencing
Liver Neoplasms
Tumor Suppressor Genes
Folic Acid
Liver Cirrhosis
Methionine
Rodentia
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Esfandiari, F., Green, R., Cotterman, R. F., Pogribny, I. P., James, S. J., & Miller, J. W. (2003). Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver. Carcinogenesis, 24(12), 1935-1940. https://doi.org/10.1093/carcin/bgg163

Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver. / Esfandiari, Farah; Green, Ralph; Cotterman, Rebecca F.; Pogribny, Igor P.; James, S. Jill; Miller, Joshua W.

In: Carcinogenesis, Vol. 24, No. 12, 12.2003, p. 1935-1940.

Research output: Contribution to journalArticle

Esfandiari, F, Green, R, Cotterman, RF, Pogribny, IP, James, SJ & Miller, JW 2003, 'Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver', Carcinogenesis, vol. 24, no. 12, pp. 1935-1940. https://doi.org/10.1093/carcin/bgg163
Esfandiari, Farah ; Green, Ralph ; Cotterman, Rebecca F. ; Pogribny, Igor P. ; James, S. Jill ; Miller, Joshua W. / Methyl deficiency causes reduction of the methyl-CpG-binding protein, MeCP2, in rat liver. In: Carcinogenesis. 2003 ; Vol. 24, No. 12. pp. 1935-1940.
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