RGD Reference Report - Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain.

Authors: Davison, JM  Mellott, TJ  Kovacheva, VP  Blusztajn, JK 
Citation: Davison JM, etal., J Biol Chem. 2009 Jan 23;284(4):1982-9. doi: 10.1074/jbc.M807651200. Epub 2008 Nov 10.
RGD ID: 9589167
Pubmed: PMID:19001366   (View Abstract at PubMed)
PMCID: PMC2629111   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M807651200   (Journal Full-text)

Choline is an essential nutrient that, via its metabolite betaine, serves as a donor of methyl groups used in fetal development to establish the epigenetic DNA and histone methylation patterns. Supplementation with choline during embryonic days (E) 11-17 in rats improves memory performance in adulthood and protects against age-related memory decline, whereas choline deficiency impairs certain cognitive functions. We previously reported that global and gene-specific DNA methylation increased in choline-deficient fetal brain and liver, and these changes in DNA methylation correlated with an apparently compensatory up-regulation of the expression of DNA methyltransferase Dnmt1. In the current study, pregnant rats were fed a diet containing varying amounts of choline (mmol/kg: 0 (deficient), 8 (control), or 36 (supplemented)) during E11-17, and indices of histone methylation were assessed in liver and frontal cortex on E17. The mRNA and protein expression of histone methyltransferases G9a and Suv39h1 were directly related to the availability of choline. DNA methylation of the G9a and Suv39h1 genes was up-regulated by choline deficiency, suggesting that the expression of these enzymes is under negative control by methylation of their genes. The levels of H3K9Me2 and H3K27Me3, tags of transcriptionally repressed chromatin, were up-regulated by choline supplementation, whereas the levels of H3K4Me2, associated with active promoters, were highest in choline-deficient rats. These data show that maternal choline supply during pregnancy modifies fetal histone and DNA methylation, suggesting that a concerted epigenomic mechanism contributes to the long term developmental effects of varied choline intake in utero.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to nutrient levels  IEP 9589167; 9589167 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ehmt2  (euchromatic histone lysine methyltransferase 2)
Suv39h1  (SUV39H1 histone lysine methyltransferase)

Objects referenced in this article
Gene Suv39h1-ps1 SUV39H1 histone lysine methyltransferase, pseudogene 1 Rattus norvegicus

Additional Information