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Series GSE60070 Query DataSets for GSE60070
Status Public on Mar 12, 2015
Title Length-dependent gene misregulation in Rett syndrome (Dnmt3a)
Organism Mus musculus
Experiment type Expression profiling by array
Summary Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that is proposed to function as a transcriptional repressor, but, despite numerous studies examining neuronal gene expression in MeCP2 mutants, no coherent model has emerged for how MeCP2 regulates transcription. Here we identify a genome-wide length-dependent increase in the expression of long genes in neurons lacking MeCP2. This gene misregulation occurs in human RTT brains and correlates with onset and severity of phenotypes in Mecp2 mutant mice, suggesting that the disruption of long gene expression contributes to RTT pathology. We present evidence that MeCP2 represses long genes by binding to brain-enriched, methylated CA dinucleotides within genes and show that loss of methylated CA in the brain recapitulates gene expression defects observed in MeCP2 mutants. We find that long genes encode proteins with neuronal functions, and overlap substantially with genes that have been implicated in autism and Fragile X syndrome. Reversing the overexpression of long genes in neurons lacking MeCP2 can improve some RTT-associated cellular deficits. These findings suggest that a function of MeCP2 in the mammalian brain is to temper the expression of genes in a length-dependent manner, and that mutations in MeCP2 and possibly other autism genes may cause neurological dysfunction by disrupting the expression of long genes in the brain.
 
Overall design Total RNA was extracted from the cerebellum of 10-11 week old Dnmt3a conditional knockout and control animals. Gene expression was analyzed using the Affymetrix Mo_Exon ST 1.0 microarray platform.
 
Contributor(s) Gabel HW, Kinde BZ, Greenberg ME
Citation(s) 25762136
Submission date Aug 04, 2014
Last update date Mar 06, 2018
Contact name Harrison Wren Gabel
E-mail(s) gabelh@pcg.wustl.edu
Organization name Harvard Medical School
Department Neurbiology
Lab Michael Greenberg
Street address 220 longwood avenue
City brookline
State/province Massachusetts
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL6096 [MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version]
Samples (6)
GSM1464557 CB_WT_d3a_1
GSM1464558 CB_WT_d3a_2
GSM1464559 CB_WT_d3a_3
This SubSeries is part of SuperSeries:
GSE60077 Length-dependent gene misregulation in Rett syndrome
Relations
BioProject PRJNA257419

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60070_RAW.tar 145.2 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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