PMID- 12586828
OWN - NLM
STAT- MEDLINE
DCOM- 20030716
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 17
DP  - 2003 Apr 25
TI  - Role of histone methyltransferase G9a in CpG methylation of the Prader-Willi 
      syndrome imprinting center.
PG  - 14996-5000
AB  - Imprinted genes in mammals are often located in clusters whose imprinting is 
      subject to long range regulation by cis-acting sequences known as imprinting 
      centers (ICs). The mechanisms by which these ICs exert their effects is unknown. 
      The Prader-Willi syndrome IC (PWS-IC) on human chromosome 15 and mouse chromosome 
      7 regulates imprinted gene expression bidirectionally within an approximately 
      2-megabase region and shows CpG methylation and histone H3 Lys-9 methylation in 
      somatic cells specific for the maternal chromosome. Here we show that histone H3 
      Lys-9 methylation of the PWS-IC is reduced in mouse embryonic stem (ES) cells 
      lacking the G9a histone H3 Lys-9/Lys-27 methyltransferase and that maintenance of 
      CpG methylation of the PWS-IC in mouse ES cells requires the function of G9a. We 
      show by RNA fluorescence in situ hybridization (FISH) that expression of Snrpn, 
      an imprinted gene regulated by the PWS-IC, is biallelic in G9a -/- ES cells, 
      indicating loss of imprinting. By contrast, Dnmt1 -/- ES cells lack CpG 
      methylation of the PWS-IC but have normal levels of H3 Lys-9 methylation of the 
      PWS-IC and show normal monoallelic Snrpn expression. Our results demonstrate a 
      role for histone methylation in the maintenance of parent-specific CpG 
      methylation of imprinting regulatory regions and suggest a possible role of 
      histone methylation in establishment of these CpG methylation patterns.
FAU - Xin, Zhenghan
AU  - Xin Z
AD  - Departments of Biochemistry and Molecular Genetics and Pediatrics, University of 
      Virginia, Charlottesville, Virginia 22908-0733, USA.
FAU - Tachibana, Makoto
AU  - Tachibana M
FAU - Guggiari, Michele
AU  - Guggiari M
FAU - Heard, Edith
AU  - Heard E
FAU - Shinkai, Yoichi
AU  - Shinkai Y
FAU - Wagstaff, Joseph
AU  - Wagstaff J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030213
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Autoantigens)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (Histones)
RN  - 0 (Repressor Proteins)
RN  - 0 (Ribonucleoproteins, Small Nuclear)
RN  - 0 (SNRPN protein, human)
RN  - 0 (snRNP Core Proteins)
RN  - 2382-65-2 (cytidylyl-3'-5'-guanosine)
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.- (Protein Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
SB  - IM
MH  - Animals
MH  - Autoantigens
MH  - Cell Line
MH  - *DNA Methylation
MH  - Dinucleoside Phosphates/*metabolism
MH  - Embryo, Mammalian
MH  - *Genomic Imprinting
MH  - Histone Methyltransferases
MH  - *Histone-Lysine N-Methyltransferase
MH  - Histones/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Methyltransferases/*physiology
MH  - Mice
MH  - Prader-Willi Syndrome/*genetics
MH  - Protein Methyltransferases
MH  - Repressor Proteins/physiology
MH  - Ribonucleoproteins, Small Nuclear/metabolism
MH  - Stem Cells/metabolism
MH  - Transgenes
MH  - snRNP Core Proteins
EDAT- 2003/02/15 04:00
MHDA- 2003/07/17 05:00
CRDT- 2003/02/15 04:00
PHST- 2003/02/15 04:00 [pubmed]
PHST- 2003/07/17 05:00 [medline]
PHST- 2003/02/15 04:00 [entrez]
AID - S0021-9258(19)30300-X [pii]
AID - 10.1074/jbc.M211753200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Apr 25;278(17):14996-5000. doi: 10.1074/jbc.M211753200. Epub 
      2003 Feb 13.