Cell-type-specific repression by methyl-CpG-binding protein 2 is biased toward long genes

K Sugino, CM Hempel, BW Okaty… - Journal of …, 2014 - Soc Neuroscience
K Sugino, CM Hempel, BW Okaty, HA Arnson, S Kato, VS Dani, SB Nelson
Journal of Neuroscience, 2014Soc Neuroscience
Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome and related
autism spectrum disorders. MeCP2 is believed to be required for proper regulation of brain
gene expression, but prior microarray studies in Mecp2 knock-out mice using brain tissue
homogenates have revealed only subtle changes in gene expression (;;;). Here, by profiling
discrete subtypes of neurons we uncovered more dramatic effects of MeCP2 on gene
expression, overcoming the “dilution problem” associated with assaying homogenates of …
Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome and related autism spectrum disorders . MeCP2 is believed to be required for proper regulation of brain gene expression, but prior microarray studies in Mecp2 knock-out mice using brain tissue homogenates have revealed only subtle changes in gene expression (; ; ; ). Here, by profiling discrete subtypes of neurons we uncovered more dramatic effects of MeCP2 on gene expression, overcoming the “dilution problem” associated with assaying homogenates of complex tissues. The results reveal misregulation of genes involved in neuronal connectivity and communication. Importantly, genes upregulated following loss of MeCP2 are biased toward longer genes but this is not true for downregulated genes, suggesting MeCP2 may selectively repress long genes. Because genes involved in neuronal connectivity and communication, such as cell adhesion and cell–cell signaling genes, are enriched among longer genes, their misregulation following loss of MeCP2 suggests a possible etiology for altered circuit function in Rett syndrome.
Soc Neuroscience