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Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation

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Abstract

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

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Abbreviations

eIF-2α :

Eukaryotic initiation factor 2α

FISH :

Fluorescence in situ hybridization

LSC :

Laser scanning cytometry

MeCP2 :

Methyl CpG-binding protein 2

RTT :

Rett syndrome

UTR :

Untranslated region

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Acknowledgements

We thank J. Ngai and T. Simcox for technical assistance, D. Rocke for statistical interpretation, and M. Mudryj and D. Yasui for critical reading of the manuscript. This work was supported in part by the NIH (1R21CA78851-01 and 1R01HD/NS41462-01A1), the Rett Syndrome Research Foundation, and the U.C. Davis M.I.N.D. Institute. Tissue samples were obtained from the University of Maryland Brain and Tissue Bank for Developmental Disorders, which is supported by NIH NO1-HD-1-3138. The experiments in this study comply with all United States and NIH human subjects guidelines.

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  1. Medical Microbiology and Immunology, Rowe Program in Human Genetics, School of Medicine , University of California, One Shields Ave., Davis, CA 95616, USA

    Damina Balmer, Jared Goldstine, Y. Manjula Rao & Janine M. LaSalle

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  1. Damina Balmer
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  2. Jared Goldstine
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  3. Y. Manjula Rao
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  4. Janine M. LaSalle
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Correspondence to Janine M. LaSalle.

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Balmer, D., Goldstine, J., Rao, Y.M. et al. Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation. J Mol Med 81, 61–68 (2003). https://doi.org/10.1007/s00109-002-0396-5

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  • DOI: https://doi.org/10.1007/s00109-002-0396-5

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