PMID- 22783988
OWN - NLM
STAT- MEDLINE
DCOM- 20130109
LR  - 20231213
IS  - 1471-2121 (Electronic)
IS  - 1471-2121 (Linking)
VI  - 13
DP  - 2012 Jul 11
TI  - Knock-down of methyl CpG-binding protein 2 (MeCP2) causes alterations in cell 
      proliferation and nuclear lamins expression in mammalian cells.
PG  - 19
LID - 10.1186/1471-2121-13-19 [doi]
AB  - BACKGROUND: MeCP2 (CpG-binding protein 2) is a nuclear multifunctional protein 
      involved in several cellular processes, like large-scale chromatin reorganization 
      and architecture, and transcriptional regulation. In recent years, a non-neuronal 
      role for MeCP2 has emerged in cell growth and proliferation. Mutations in the 
      MeCP2 gene have been reported to determine growth disadvantages in cultured 
      lymphocyte cells, and its functional ablation suppresses cell growth in glial 
      cells and proliferation in mesenchymal stem cells and prostate cancer cells. 
      MeCP2 interacts with lamin B receptor (LBR) and with Heterochromatin Protein 1 
      (HP1) at the nuclear envelope (NE), suggesting that it could be part of complexes 
      involved in attracting heterochromatin at the nuclear periphery and in mediating 
      gene silencing. The nuclear lamins, major components of the lamina, have a role 
      in maintaining NE integrity, in orchestrating mitosis, in DNA replication and 
      transcription, in regulation of mitosis and apoptosis and in providing anchoring 
      sites for chromatin domains.In this work, we inferred that MeCP2 might have a 
      role in nuclear envelope stability, thereby affecting the proliferation pattern 
      of highly proliferating systems. RESULTS: By performing knock-down (KD) of MeCP2 
      in normal murine (NIH-3 T3) and in human prostate transformed cells (PC-3 and 
      LNCaP), we observed a strong proliferation decrease and a defect in the cell 
      cycle progression, with accumulation of cells in S/G2M, without triggering a 
      strong apoptotic and senescent phenotype. In these cells, KD of MeCP2 evidenced a 
      considerable decrease of the levels of lamin A, lamin C, lamin B1 and LBR 
      proteins. Moreover, by confocal analysis we confirmed the reduction of lamin A 
      levels, but we also observed an alteration in the shape of the nuclear lamina and 
      an irregular nuclear rim. CONCLUSIONS: Our results that indicate reduced levels 
      of NE components, are consistent with a hypothesis that the deficiency of MeCP2 
      might cause the lack of a key "bridge" function that links the peripheral 
      heterochromatin to the NE, thereby causing an incorrect assembly of the NE 
      itself, together with a decreased cell proliferation and viability.
FAU - Babbio, Federica
AU  - Babbio F
AD  - Department of Theoretical and Applied Sciences, Insubria University, via A, da 
      Giussano 10, Busto Arsizio, 21052, Italy. feba0612@libero.it
FAU - Castiglioni, Ilaria
AU  - Castiglioni I
FAU - Cassina, Chiara
AU  - Cassina C
FAU - Gariboldi, Marzia Bruna
AU  - Gariboldi MB
FAU - Pistore, Christian
AU  - Pistore C
FAU - Magnani, Elena
AU  - Magnani E
FAU - Badaracco, Gianfranco
AU  - Badaracco G
FAU - Monti, Elena
AU  - Monti E
FAU - Bonapace, Ian Marc
AU  - Bonapace IM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120711
PL  - England
TA  - BMC Cell Biol
JT  - BMC cell biology
JID - 100966972
RN  - 0 (Lamin Type A)
RN  - 0 (Lamin Type B)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (lamin C)
SB  - IM
MH  - Animals
MH  - Cell Cycle Checkpoints
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Humans
MH  - Lamin Type A/*metabolism
MH  - Lamin Type B/*metabolism
MH  - Methyl-CpG-Binding Protein 2/*antagonists & inhibitors/genetics/metabolism
MH  - Mice
MH  - NIH 3T3 Cells
MH  - Nuclear Envelope/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Lamin B Receptor
PMC - PMC3477090
EDAT- 2012/07/13 06:00
MHDA- 2013/01/10 06:00
PMCR- 2012/07/11
CRDT- 2012/07/13 06:00
PHST- 2012/02/13 00:00 [received]
PHST- 2012/07/03 00:00 [accepted]
PHST- 2012/07/13 06:00 [entrez]
PHST- 2012/07/13 06:00 [pubmed]
PHST- 2013/01/10 06:00 [medline]
PHST- 2012/07/11 00:00 [pmc-release]
AID - 1471-2121-13-19 [pii]
AID - 10.1186/1471-2121-13-19 [doi]
PST - epublish
SO  - BMC Cell Biol. 2012 Jul 11;13:19. doi: 10.1186/1471-2121-13-19.