PMID- 17625110
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20220317
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 77
IP  - 4
DP  - 2007 Oct
TI  - Promoter methylation regulates estrogen receptor 2 in human endometrium and 
      endometriosis.
PG  - 681-7
AB  - Steroid receptors in the stromal cells of endometrium and its disease counterpart 
      tissue endometriosis play critical physiologic roles. We found that mRNA and 
      protein levels of estrogen receptor 2 (ESR2) were strikingly higher, whereas 
      levels of estrogen receptor 1 (ESR1), total progesterone receptor (PGR), and 
      progesterone receptor B (PGR B) were significantly lower in endometriotic versus 
      endometrial stromal cells. Because ESR2 displayed the most striking levels of 
      differential expression between endometriotic and endometrial cells, and the 
      mechanisms for this difference are unknown, we tested the hypothesis that 
      alteration in DNA methylation is a mechanism responsible for severely increased 
      ESR2 mRNA levels in endometriotic cells. We identified a CpG island occupying the 
      promoter region (-197/+359) of the ESR2 gene. Bisulfite sequencing of this region 
      showed significantly higher methylation in primary endometrial cells (n = 8 
      subjects) versus endometriotic cells (n = 8 subjects). The demethylating agent 
      5-aza-2'-deoxycytidine significantly increased ESR2 mRNA levels in endometrial 
      cells. Mechanistically, we employed serial deletion mutants of the ESR2 promoter 
      fused to the luciferase reporter gene and transiently transfected into both 
      endometriotic and endometrial cells. We demonstrated that the critical region 
      (-197/+372) that confers promoter activity also bears the CpG island, and the 
      activity of the ESR2 promoter was strongly inactivated by in vitro methylation. 
      Taken together, methylation of a CpG island at the ESR2 promoter region is a 
      primary mechanism responsible for differential expression of ESR2 in 
      endometriosis and endometrium. These findings may be applied to a number of areas 
      ranging from diagnosis to the treatment of endometriosis.
FAU - Xue, Qing
AU  - Xue Q
AD  - Division of Reproductive Biology Research, Department of Obsterics and 
      Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, 
      Illinois 60611, USA.
FAU - Lin, Zhihong
AU  - Lin Z
FAU - Cheng, You-Hong
AU  - Cheng YH
FAU - Huang, Chiang-Ching
AU  - Huang CC
FAU - Marsh, Erica
AU  - Marsh E
FAU - Yin, Ping
AU  - Yin P
FAU - Milad, Magdy P
AU  - Milad MP
FAU - Confino, Edmond
AU  - Confino E
FAU - Reierstad, Scott
AU  - Reierstad S
FAU - Innes, Joy
AU  - Innes J
FAU - Bulun, Serdar E
AU  - Bulun SE
LA  - eng
GR  - U54-HD40093/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070711
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (progesterone receptor B)
RN  - 776B62CQ27 (Decitabine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adult
MH  - Azacitidine/analogs & derivatives/pharmacology
MH  - Cells, Cultured
MH  - CpG Islands
MH  - *DNA Methylation
MH  - Decitabine
MH  - Endometriosis/*genetics
MH  - Endometrium/drug effects/*metabolism
MH  - Estrogen Receptor alpha/genetics
MH  - Estrogen Receptor beta/*genetics
MH  - Female
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - Promoter Regions, Genetic/drug effects
MH  - RNA, Messenger/analysis/metabolism
MH  - Receptors, Progesterone/genetics
MH  - Stromal Cells/drug effects/metabolism
EDAT- 2007/07/13 09:00
MHDA- 2007/11/14 09:00
CRDT- 2007/07/13 09:00
PHST- 2007/07/13 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/07/13 09:00 [entrez]
AID - biolreprod.107.061804 [pii]
AID - 10.1095/biolreprod.107.061804 [doi]
PST - ppublish
SO  - Biol Reprod. 2007 Oct;77(4):681-7. doi: 10.1095/biolreprod.107.061804. Epub 2007 
      Jul 11.