PMID- 21951854
OWN - NLM
STAT- MEDLINE
DCOM- 20111212
LR  - 20111017
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 414
IP  - 1
DP  - 2011 Oct 14
TI  - The involvement of DNA and histone methylation in the repression of IL-1beta-induced 
      MCP-1 production by hypoxia.
PG  - 252-8
LID - 10.1016/j.bbrc.2011.09.066 [doi]
AB  - Hypoxia is a microenvironmental pathophysiologic factor commonly associated with 
      tumors and tissue inflammation. We previously reported that hypoxia repressed 
      IL-1beta-induced monocyte chemoattractant protein-1 (MCP-1) expression. The purpose 
      of this study was to investigate the mechanisms involved in the repression of 
      MCP-1 expression under hypoxia. Treatment of HeLa cells with 5-aza-dC, an 
      inhibitor of DNA methylation, abolished the repression of IL-1beta-induced MCP-1 
      expression by hypoxia. A detailed study of the methylation of CpGs sites using 
      bisulfite-sequencing PCR and 5-methylcytosine immunoprecipitation showed that 
      hypoxia induced DNA methylation in both the enhancer and promoter regions of 
      MCP-1in IL-1beta-treated cells. Next, we analyzed histone methylation within the 
      MCP-1 promoter and enhancer regions. The level of H3K9 di-methylation, a mark of 
      gene repression, in both promoter and enhancer regions was increased by hypoxia 
      in IL-1beta-treated cells. Our findings suggest that changes in the methylation 
      status of CpGs, as well as histone 3 methylation, may represent a critical event 
      in transcriptional repression of IL-1beta-induced MCP-1 expression by hypoxia. 
      Therefore, DNA methylation is associated with not only epigenetic gene silencing, 
      but also with transient transcriptional repression.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Aoi, Yoko
AU  - Aoi Y
AD  - Department of Cellular Physiological Chemistry, Tokyo Medical and Dental 
      University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
FAU - Nakahama, Ken-ichi
AU  - Nakahama K
FAU - Morita, Ikuo
AU  - Morita I
FAU - Safronova, Olga
AU  - Safronova O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110917
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Histones)
RN  - 0 (Interleukin-1beta)
SB  - IM
MH  - Cell Hypoxia/genetics
MH  - Chemokine CCL2/*genetics
MH  - CpG Islands
MH  - *DNA Methylation
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Gene Silencing
MH  - HeLa Cells
MH  - Histones/*metabolism
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Methylation
MH  - Transcription, Genetic
MH  - Tumor Microenvironment/*genetics
EDAT- 2011/09/29 06:00
MHDA- 2011/12/14 06:00
CRDT- 2011/09/29 06:00
PHST- 2011/09/12 00:00 [received]
PHST- 2011/09/14 00:00 [accepted]
PHST- 2011/09/29 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
AID - S0006-291X(11)01670-6 [pii]
AID - 10.1016/j.bbrc.2011.09.066 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2011 Oct 14;414(1):252-8. doi: 
      10.1016/j.bbrc.2011.09.066. Epub 2011 Sep 17.