Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development.
MeCP2 plays a critical role in interpreting epigenetic signatures that command chromatin conformation and regulation of gene transcription. In spite of MeCP2's ubiquitous expression, its functions have always been considered in the context of brain physiology. In this study, we demonstrate that alterations of the normal pattern of expression of MeCP2 in cardiac and skeletal tissues are detrimental for normal development. Overexpression of MeCP2 in the mouse heart leads to embryonic lethality with cardiac septum hypertrophy and dysregulated expression of MeCP2 in skeletal tissue produces severe malformations. We further show that MeCP2's expression in the heart is developmentally regulated; further suggesting that it plays a key role in regulating transcriptional programs in non-neural tissues.
Alvarez-Saavedra
Matías
M
Centro de Estudios Científicos, Valdivia 5110246, Chile.
Carrasco
Loreto
L
Sura-Trueba
Sylvia
S
Demarchi Aiello
Vera
V
Walz
Katherina
K
Neto
José Xavier
JX
Young
Juan I
JI
D000423:Alcian Blue; D000818:Animals; D000880:Anthraquinones; D001842:Bone and Bones / Q000196:embryology / Q000378:metabolism*; D001973:Bromodeoxyuridine; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes / Q000235:genetics
D000880:Anthraquinones; D017931:DNA Primers; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; C010078:alizarin; D001973:Bromodeoxyuridine; D000423:Alcian Blue