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Partial silencing of methyl cytosine protein binding 2 ( MECP2 ) in mesenchymal stem cells induces senescence with an increase in damaged DNA
Author(s) -
Squillaro Tiziana,
Alessio Nicola,
Cipollaro Marilena,
Renieri Alessandra,
Giordano Antonio,
Galderisi Umberto
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-143057
Subject(s) - dna methylation , gene silencing , epigenetics , mecp2 , microbiology and biotechnology , biology , telomerase , cpg site , methylation , chemistry , dna , genetics , gene , gene expression , phenotype
DNA methylation is an epigenetic modification that occurs almost exclusively on CpG dinucleotides. MECP2 is a member of a family of proteins that preferentially bind to methylated CpGs. We analyzed the contribution of MECP2 to the physiology of mesenchymal stem cells (MSCs). Partial silencing of MECP2 in human MSCs induced a significant reduction of S‐phase cells, along with an increase in G 1 cells. These changes were accompanied by a reduction of apoptosis, the triggering of senescence, a decrease in telomerase activity, and the down‐regulation of genes involved in maintaining stem cell properties. Senescence appeared to rely on impairment of DNA damage repair and seemed to occur through RB‐ and P53‐related pathways. The effects of MECP2 silencing could be related to the modification of the DNA methylation status. Our results indicate that the silencing of MECP2 induces an increase in methylated cytosines in the genome. Nevertheless, MECP2 partial silencing did not change the methylation of promoters, whose expression is affected by MECP2 down‐regulation.—Squillaro, T., Alessio, N., Cipollaro, M., Renieri, A., Giordano, A., Galderisi, U. Partial silencing of methyl cytosine protein binding 2 ( MECP2 ) in mesenchymal stem cells induces senescence with an increase in damaged DNA FASEB J. 24, 1593–1603 (2010). www.fasebj.org