PMID- 15689352
OWN - NLM
STAT- MEDLINE
DCOM- 20050728
LR  - 20071114
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 14
IP  - 6
DP  - 2005 Mar 15
TI  - Homologous pairing of 15q11-13 imprinted domains in brain is developmentally 
      regulated but deficient in Rett and autism samples.
PG  - 785-97
AB  - Rett syndrome (RTT), caused by mutations in MECP2 (encoding methyl CpG binding 
      protein 2), and Angelman syndrome (AS), caused by maternal deficiency of 
      chromosome 15q11-13, are autism-spectrum neurodevelopmental disorders. MeCP2 is a 
      transcriptional repressor of methylated genes, but MECP2 mutation does not 
      directly affect the imprinted expression of genes within 15q11-13. We tested a 
      potential role for MeCP2 in the homologous pairing of imprinted 15q11-13 alleles 
      in human brain tissue and differentiated neurons by fluorescence in situ 
      hybridization (FISH). FISH analysis of control cerebral samples demonstrated a 
      significant increase in homologous pairing specific to chromosome 15 from infant 
      to juvenile brain samples. Significant and specific deficiencies in the 
      percentage of paired chromosome 15 alleles were observed in RTT, AS and autism 
      brain samples when compared with normal controls. SH-SY5Y neuroblastoma cells 
      also showed a significant and specific increase in the percentage of chromosome 
      15q11-13 paired alleles following induced differentiation in vitro. Transfection 
      with a methylated oligonucleotide decoy specifically blocked binding of MeCP2 to 
      the SNURF/SNRPN promoter within 15q11-13 and significantly lowered the percentage 
      of paired 15q11-13 alleles in SH-SY5Y cells. These combined results suggest a 
      role for MeCP2 in chromosome organization in the developing brain and provide a 
      potential mechanistic association between several related neurodevelopmental 
      disorders.
FAU - Thatcher, Karen N
AU  - Thatcher KN
AD  - Medical Microbiology and Immunology and Rowe Program in Human Genetics, School of 
      Medicine, University of California, Davis, CA 95616, USA.
FAU - Peddada, Sailaja
AU  - Peddada S
FAU - Yasui, Dag H
AU  - Yasui DH
FAU - Lasalle, Janine M
AU  - Lasalle JM
LA  - eng
GR  - 1R01HD/NS41462/HD/NICHD NIH HHS/United States
GR  - MH/NS 31862/MH/NIMH NIH HHS/United States
GR  - N01-HD-1-3138/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050202
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MECP2 protein, human)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Repressor Proteins)
SB  - IM
MH  - Autistic Disorder/genetics/*metabolism
MH  - Brain/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Chromosomal Proteins, Non-Histone/genetics/*metabolism
MH  - *Chromosome Pairing/genetics
MH  - Chromosomes, Human, Pair 15/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Methyl-CpG-Binding Protein 2
MH  - Neurons/metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Rett Syndrome/genetics/*metabolism
EDAT- 2005/02/04 09:00
MHDA- 2005/07/29 09:00
CRDT- 2005/02/04 09:00
PHST- 2005/02/04 09:00 [pubmed]
PHST- 2005/07/29 09:00 [medline]
PHST- 2005/02/04 09:00 [entrez]
AID - ddi073 [pii]
AID - 10.1093/hmg/ddi073 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2005 Mar 15;14(6):785-97. doi: 10.1093/hmg/ddi073. Epub 2005 Feb 
      2.