PMID- 22865604
OWN - NLM
STAT- MEDLINE
DCOM- 20130131
LR  - 20211021
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 30
IP  - 10
DP  - 2012 Oct
TI  - Disease modeling using embryonic stem cells: MeCP2 regulates nuclear size and RNA 
      synthesis in neurons.
PG  - 2128-39
LID - 10.1002/stem.1180 [doi]
AB  - Mutations in the gene encoding the methyl-CpG-binding protein MECP2 are the major 
      cause of Rett syndrome, an autism spectrum disorder mainly affecting young 
      females. MeCP2 is an abundant chromatin-associated protein, but how and when its 
      absence begins to alter brain function is still far from clear. Using a stem 
      cell-based system allowing the synchronous differentiation of neuronal 
      progenitors, we found that in the absence of MeCP2, the size of neuronal nuclei 
      fails to increase at normal rates during differentiation. This is accompanied by 
      a marked decrease in the rate of ribonucleotide incorporation, indicating an 
      early role of MeCP2 in regulating total gene transcription, not restricted to 
      selected mRNAs. We also found that the levels of brain-derived neurotrophic 
      factor (BDNF) were decreased in mutant neurons, while those of the presynaptic 
      protein synaptophysin increased at similar rates in wild-type and mutant neurons. 
      By contrast, nuclear size, transcription rates, and BDNF levels remained 
      unchanged in astrocytes lacking MeCP2. Re-expressing MeCP2 in mutant neurons 
      rescued the nuclear size phenotype as well as BDNF levels. These results reveal a 
      new role of MeCP2 in regulating overall RNA synthesis in neurons during the 
      course of their maturation, in line with recent findings indicating a reduced 
      nucleolar size in neurons of the developing brain of mice lacking Mecp2.
CI  - Copyright (c) 2012 AlphaMed Press.
FAU - Yazdani, Morteza
AU  - Yazdani M
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Deogracias, Ruben
AU  - Deogracias R
FAU - Guy, Jacky
AU  - Guy J
FAU - Poot, Raymond A
AU  - Poot RA
FAU - Bird, Adrian
AU  - Bird A
FAU - Barde, Yves-Alain
AU  - Barde YA
LA  - eng
GR  - 092076/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Mecp2 protein, mouse)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cell Differentiation
MH  - Cell Nucleus Size/*genetics
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Embryonic Stem Cells/*metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Genetic Vectors
MH  - Humans
MH  - Lentivirus
MH  - Methyl-CpG-Binding Protein 2/*genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*metabolism/pathology
MH  - RNA, Messenger/*biosynthesis
MH  - Rett Syndrome/genetics/*metabolism/pathology
MH  - Transcription, Genetic
MH  - Transfection
EDAT- 2012/08/07 06:00
MHDA- 2013/02/01 06:00
CRDT- 2012/08/07 06:00
PHST- 2012/08/07 06:00 [entrez]
PHST- 2012/08/07 06:00 [pubmed]
PHST- 2013/02/01 06:00 [medline]
AID - 10.1002/stem.1180 [doi]
PST - ppublish
SO  - Stem Cells. 2012 Oct;30(10):2128-39. doi: 10.1002/stem.1180.