Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation.
Rett syndrome is caused by mutations in MECP2 and characterized by arrested postnatal neurodevelopment. MECP2 is ubiquitously expressed, but its protein product, methyl-CpG-binding protein 2 (MeCP2), is highly expressed in a subpopulation of cells in the adult brain. Automated quantitation of MeCP2 expression on a human developmental tissue microarray was performed by laser scanning cytometry. A significant correlation between age and MeCP2 level, population heterogeneity, and percentage of MeCP2 high-expressing cells was specifically observed in cerebral but not renal samples. In contrast, an inverse correlation between use of the long 3' UTR of MECP2 and age was observed, suggesting that an acquired switch in polyadenylation is responsible for the elevated MeCP2. Acquired elevated MeCP2 expression in neurons beginning in infancy and progressing through childhood may explain the delayed onset and developmental arrest of Rett syndrome
Balmer
Damina
D
Medical Microbiology and Immunology, Rowe Program in Human Genetics, School of Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA.
Goldstine
Jared
J
Rao
Y Manjula
YM
LaSalle
Janine M
JM
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005333:Fetus; D006801:Humans; D007223:Infant; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D009474:Neurons / Q000378:metabolism; D026723:Polyadenylation; D012097:Repressor Proteins / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins