PMID- 22491064
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20150727
IS  - 1559-2308 (Electronic)
IS  - 1559-2294 (Linking)
VI  - 7
IP  - 5
DP  - 2012 May
TI  - Epigenetic regulation of glucocorticoid receptor expression in aorta from mice 
      with hyperhomocysteinemia.
PG  - 514-21
LID - 10.4161/epi.19836 [doi]
AB  - Hyperhomocysteinemia (HHcy) is a risk factor for vascular disease but its 
      underlying molecular pathology is not understood. Homocysteine is metabolically 
      linked to the epigenetic process of DNA methylation. Tissue-specific changes in 
      DNA methylation have been observed in HHcy but little is known about vascular 
      tissue. The objective of this study was to determine if changes in the epigenetic 
      regulation of glucocorticoid receptor (GR) expression (encoded by Nr3c1) in aorta 
      are associated with HHcy. C57BL/6 mice heterozygous for disruption of the 
      cystathionine-beta-synthase gene (Cbs+/-) and controls (Cbs+/+) were fed a control 
      or high methionine/low folate (HH) diet to induce HHcy. Cbs+/- and Cbs+/+ fed the 
      HH diet had higher plasma total homocysteine levels (19.9 +/- 3.2 and 7.0 +/- 0.9 muM, 
      respectively) than Cbs+/+ mice fed the control diet (2.7 +/- 0.2 muM), and this was 
      accompanied by lower Nr3c1 mRNA and lower GR protein in aorta. The Nr3c1 gene 
      contains multiple first exons producing heterogeneous RNA transcripts expressed 
      in a tissue-specific manner. We identified expression of two transcripts in 
      aorta. Bisulfite pyrosequencing found increased methylation of the promoter 
      regions for these transcripts at sites corresponding to Sp1 and Nrf1 binding 
      sites. Chromatin immunoprecipitation found lower binding of Nrf1 to the Nr3c1 
      promoter but higher expression of Nrf1 protein in aorta from mice with HHcy. 
      These findings show methylation and silencing of vascular Nr3c1 expression and 
      suggest a role for epigenetic regulation of gene expression in HHcy.
FAU - Sulistyoningrum, Dian C
AU  - Sulistyoningrum DC
AD  - Department of Pathology and Laboratory Medicine, Child and Family Research 
      Institute, University of British Columbia, Vancouver, BC, Canada.
FAU - Singh, Ranji
AU  - Singh R
FAU - Devlin, Angela M
AU  - Devlin AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120501
PL  - United States
TA  - Epigenetics
JT  - Epigenetics
JID - 101265293
RN  - 0 (Nrf1 protein, mouse)
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism/*pathology
MH  - Binding Sites
MH  - Chromatin Immunoprecipitation
MH  - Cystathionine beta-Synthase/genetics/metabolism
MH  - *DNA Methylation
MH  - Diet
MH  - *Epigenesis, Genetic
MH  - Heterozygote
MH  - Homocysteine/blood/genetics
MH  - Hyperhomocysteinemia/*genetics/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nuclear Respiratory Factor 1/genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Glucocorticoid/genetics/*metabolism
MH  - Sequence Analysis, DNA/methods
EDAT- 2012/04/12 06:00
MHDA- 2012/10/12 06:00
CRDT- 2012/04/12 06:00
PHST- 2012/04/12 06:00 [entrez]
PHST- 2012/04/12 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
AID - 19836 [pii]
AID - 10.4161/epi.19836 [doi]
PST - ppublish
SO  - Epigenetics. 2012 May;7(5):514-21. doi: 10.4161/epi.19836. Epub 2012 May 1.