PMID- 23242655
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20211021
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 40
IP  - 3
DP  - 2013 Mar
TI  - Mutant p53 binds to estrogen receptor negative promoter via DNMT1 and HDAC1 in 
      MDA-MB-468 breast cancer cells.
PG  - 2617-25
LID - 10.1007/s11033-012-2348-7 [doi]
AB  - DNA methylation and histone deacetylation are two epigenetic mechanisms involved 
      in the lack of estrogen receptor (ER) expression. Our previous studies 
      demonstrated that mutant p53 along with repression complex proteins including 
      DNMT1, HDAC1 and MeCP2 is associated with ER-negative promoter in MDA-MB-468 
      cells. To elucidate the molecular mechanism of estrogen receptor 1 (ESR1) gene 
      silencing in these cells, we down-regulated DNMT1 and HDAC1 expression using 
      siRNAs and studied the ability of DNMT1, HDAC1, MeCP2 and p53 in binding to ESR1 
      promoter CpG island. Our results showed that DNMT1 or HDAC1 down-regulation 
      disassembled the repression complex proteins and mutant p53 from ER-negative 
      promoter. The partial demethylation of ESR1 promoter and ER re-expression in 
      down-regulated cells supports these findings. In vivo binding studies 
      demonstrated that mutation of p53 protein in this cell line did not affect its 
      binding capacity to DNMT1, HDAC1 and MeCP2 proteins. Our observations suggest 
      that not only histone deacetylase activity of HDAC1 contributes to inactivation 
      of methylated ESR1 gene but also HDAC1 presence on ESR1 promoter is important for 
      assembly of DNMT1 in repression complex. In addition, our data revealed that 
      mutant p53 protein binds to the promoter of ESR1 through direct interaction with 
      HDAC1 and indirect interaction with DNMT1, MeCP2 proteins in the ER-negative 
      MDA-MB-468 cells.
FAU - Arabsolghar, Rita
AU  - Arabsolghar R
AD  - Recombinant Protein Lab, Department of Biochemistry, School of Medicine, Shiraz 
      University of Medical Sciences, Shiraz, Iran.
FAU - Azimi, Tayebeh
AU  - Azimi T
FAU - Rasti, Mozhgan
AU  - Rasti M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121215
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (DNMT1 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
SB  - IM
MH  - Breast Neoplasms/*genetics/*metabolism
MH  - Cell Line, Tumor
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/genetics/*metabolism
MH  - DNA Methylation
MH  - Down-Regulation
MH  - Estrogen Receptor alpha/*genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Histone Deacetylase 1/genetics/*metabolism
MH  - Humans
MH  - MCF-7 Cells
MH  - Methyl-CpG-Binding Protein 2/metabolism
MH  - Mutation
MH  - *Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA Interference
MH  - Tumor Suppressor Protein p53/genetics/*metabolism
EDAT- 2012/12/18 06:00
MHDA- 2014/03/04 06:00
CRDT- 2012/12/18 06:00
PHST- 2012/08/02 00:00 [received]
PHST- 2012/12/09 00:00 [accepted]
PHST- 2012/12/18 06:00 [entrez]
PHST- 2012/12/18 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
AID - 10.1007/s11033-012-2348-7 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2013 Mar;40(3):2617-25. doi: 10.1007/s11033-012-2348-7. Epub 2012 
      Dec 15.