PMID- 26683811
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20210816
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 30
IP  - 3
DP  - 2016 Mar
TI  - Tissue-Specific Expression of Estrogen Receptor 1 Is Regulated by DNA Methylation 
      in a T-DMR.
PG  - 335-47
LID - 10.1210/me.2015-1058 [doi]
AB  - The mechanism controlling tissue-specific expression of estrogen receptor 1 
      (ESR1) is unclear. In other genes, DNA methylation of a region called the 
      tissue-dependent and differentially methylated region (T-DMR) has been associated 
      with tissue-specific gene expression. This study investigated whether human ESR1 
      has a T-DMR and whether DNA methylation of the T-DMR regulates its expression. 
      ESR1 expression was tissue-specific, being high in the endometrium and mammary 
      gland and low/nil in the placenta and skin. Therefore, DNA methylation profiles 
      of the promoter of ESR1 were analyzed in these tissues and in breast cancer 
      tissues. In all of the normal tissues, the proximal promoter regions were 
      unmethylated. On the other hand, the distal regions (T-DMR) were unmethylated in 
      the endometrium and mammary gland, but were moderately methylated and 
      hypermethylated in the placenta and skin, respectively. T-DMR-methylated reporter 
      assay was performed to examine whether DNA methylation at the T-DMR suppresses 
      ESR1 transcription. T-DMR, but not the promoter region, had transcriptional 
      activities and DNA methylation of the T-DMR suppressed ESR1 transcription. Early 
      growth response protein 1 was shown to be a possible transcription factor to bind 
      the T-DMR and up-regulate ESR1 expression. ESR1 has several upstream exons, and 
      each upstream exon, Exon-A/Exon-B/Exon-C, had its own T-DMR. In some breast 
      cancer cases and breast cancer cell lines, ESR1 expression was not regulated by 
      DNA methylation at T-DMR as it is in normal tissues. In conclusion, ESR1 has a 
      T-DMR. DNA methylation status at the T-DMR is involved in tissue-specific ESR1 
      expression in normal tissues but not always in breast cancer.
FAU - Maekawa, Ryo
AU  - Maekawa R
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Sato, Shun
AU  - Sato S
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Okada, Maki
AU  - Okada M
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Lee, Lifa
AU  - Lee L
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Tamura, Isao
AU  - Tamura I
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Jozaki, Kosuke
AU  - Jozaki K
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Kajimura, Takuya
AU  - Kajimura T
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Asada, Hiromi
AU  - Asada H
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Yamagata, Yoshiaki
AU  - Yamagata Y
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Tamura, Hiroshi
AU  - Tamura H
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Yamamoto, Shigeru
AU  - Yamamoto S
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
FAU - Sugino, Norihiro
AU  - Sugino N
AD  - Departments of Obstetrics and Gynecology (R.M., S.S., M.O., L.L., I.T., K.J., 
      T.K., H.A., Y.Y., H.T., N.S.) and Digestive Surgery and Surgical Oncology (S.Y.), 
      Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151218
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Histones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Base Sequence
MH  - Breast Neoplasms/genetics
MH  - DNA Methylation/*genetics
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Exons/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter
MH  - Histones/metabolism
MH  - Humans
MH  - MCF-7 Cells
MH  - Organ Specificity/*genetics
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription Factors/metabolism
PMC - PMC5414650
EDAT- 2015/12/20 06:00
MHDA- 2016/12/15 06:00
PMCR- 2017/03/01
CRDT- 2015/12/20 06:00
PHST- 2015/12/20 06:00 [entrez]
PHST- 2015/12/20 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2017/03/01 00:00 [pmc-release]
AID - ME-15-1058 [pii]
AID - 10.1210/me.2015-1058 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2016 Mar;30(3):335-47. doi: 10.1210/me.2015-1058. Epub 2015 Dec 
      18.