PMID- 18506103
OWN - NLM
STAT- MEDLINE
DCOM- 20080717
LR  - 20191110
IS  - 1341-7568 (Print)
IS  - 1341-7568 (Linking)
VI  - 83
IP  - 2
DP  - 2008 Apr
TI  - MeCP2 knockdown reveals DNA methylation-independent gene repression of target 
      genes in living cells and a bias in the cellular location of target gene 
      products.
PG  - 199-208
AB  - MeCP2, a methyl-CpG binding domain (MBD) protein, is known to bind to methylated 
      CpG sites via a conserved MBD, leading to transcriptional repression. However, 
      studies in cell-free system for gene repression and MeCP2 binding have suggested 
      that DNA methylation-independent repression also occurs in living cells. It has 
      been difficult to characterize the target genes of MeCP2 because a limited number 
      have been identified to date. In this context, we screened for MeCP2 target genes 
      using knockdown (KD) experiments combined with microarray gene expression 
      analyses. Of the 49 genes that showed a more than three-fold increase in 
      expression in two independent KD experiments conducted with different siRNA sets, 
      unexpectedly, half (24 genes) did not contain promoter CpG islands (CGIs). Of 
      seven selected genes that did contain CGIs, only two were methylated at the CGI, 
      bound MeCP2 before KD, and reduced MeCP2 after KD. For three, MeCP2 was observed 
      to bind to the unmethylated CGI before KD, and for one MeCP2 was reduced after 
      KD. Another two genes neither had DNA methylation nor bound MeCP2 before KD. Gene 
      ontology analysis suggested that MeCP2 represses a certain group of genes. These 
      results suggest that in addition to the canonical gene repression function, MeCP2 
      can repress gene expression by binding to unmethylated DNA in particular genes in 
      living cells.
FAU - Yakabe, Shinya
AU  - Yakabe S
AD  - Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, 
      Japan.
FAU - Soejima, Hidenobu
AU  - Soejima H
FAU - Yatsuki, Hitomi
AU  - Yatsuki H
FAU - Tominaga, Hirotaka
AU  - Tominaga H
FAU - Zhao, Wei
AU  - Zhao W
FAU - Higashimoto, Ken
AU  - Higashimoto K
FAU - Joh, Keiichiro
AU  - Joh K
FAU - Kudo, Shinichi
AU  - Kudo S
FAU - Miyazaki, Kohji
AU  - Miyazaki K
FAU - Mukai, Tsunehiro
AU  - Mukai T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Genes Genet Syst
JT  - Genes & genetic systems
JID - 9607822
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Cell Line
MH  - CpG Islands
MH  - *DNA Methylation
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Methyl-CpG-Binding Protein 2/antagonists & inhibitors/genetics/*metabolism
MH  - RNA Interference
MH  - Repressor Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Vocabulary, Controlled
EDAT- 2008/05/29 09:00
MHDA- 2008/07/18 09:00
CRDT- 2008/05/29 09:00
PHST- 2008/05/29 09:00 [pubmed]
PHST- 2008/07/18 09:00 [medline]
PHST- 2008/05/29 09:00 [entrez]
AID - JST.JSTAGE/ggs/83.199 [pii]
AID - 10.1266/ggs.83.199 [doi]
PST - ppublish
SO  - Genes Genet Syst. 2008 Apr;83(2):199-208. doi: 10.1266/ggs.83.199.