High-Resolution Analysis of Parent-of-Origin Allelic Expression in the Mouse Brain
Sex-Specific Parent-of-Origin Allelic Expression in the Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain Mouse BrainChristopher Gregg1,2 Jiangwen Zhang,3 James E.Butler,1,2 David Haig,4 and Catherine Dulac1,2* Mohamed Antar Aziz Mohamed Laboratory of Molecular Biology 2012310880
Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain
Introduction Introduction What is Epigenetics ?“Any process that alters gene activity without changing the DNA sequence, and leads to modifications that can be transmitted to daughter cells”
Genomic Imprinting What is Genomic Imprinting? Genomic imprinting is an epigenetic mode of gene regulation involving preferential expression of the paternally or maternally inherited allele. Why Genomic Imprinting is important?Because many imprinted genes are associated with embryonic growth, development feeding and motivated behaviors, and parental biases preferentially target genetic pathways governing metabolism and cell adhesion.
Prader-Willi/Angelman syndrome Both produced by same genetic mutation *PWS: deletion of *AS: deletion of paternal copy or UPD of maternal copy, maternal chromosome 15q11- mutation of UBE3A gene q13 or UPD of chromosome 15q11-q13 *Language, motor and developmental *Severe mental delays, excessive retardation, happy weight gain demeanor, non-verbal
Sexual dimorphism is a central characteristic of mammalianbrain function and behavior that influences major neurologicaldiseases in humans. Three processes may underlie sexually dimorphic genomic imprinting. Nonrandom X inactivation. Imprinting of individual X-linked loci in females. Autosomal genes might be imprinted in one sex but not the other.
Results ResultsImprinted gene expression in the adult CNS.
A high-resolution approach to analyze imprinting.Illumina RNA-sequencing (RNA-Seq) technology to characterize thetranscriptome of brain tissues from F1 hybrids resulting from reciprocalcrosses of CAST/EiJ (CAST) and C57BL/6J (C57) mice [F1 initial cross (F1i):CAST mother × C57 father; F1 reciprocal cross (F1r): C57 mother × CASTfather].F1i CAST (mother) X C57 (father) F1r C57 (mother) X CAST (father)
Identification of loci exhibiting parent-of-origin allelic effects in the embryonic and adult CNS using Illumina RNA-Seq.
Sex-specific imprinting and preferential expression of the Xm in the female brain.This elevated expression from the Xm versus the Xp may indicate a bias in Xinactivation in the brain, a hypothesis further investigated with a transgenic mouseline expressing X-linked egfp under the control of the cytomegalovirus (CMV)promoter as a reporter of the active X chromosome.
Preferential expression of Xm in female cortical regions indicated by Xmegfp/Xp and Xm/Xpegfp transgenic mice.Cortex
Sex-specific imprinted autosomal genes were uncovered in the adult male and female POA and mPFC.
Sex-specific imprinted expression of Mrpl48 and Il18 in the female brain.Illumina read data for an imprinted SNP in the 3′ untranslated region (3′ UTR) of Mrpl48
Illumina read data for the imprinted SNP in ll18
QPCR analysis of Il18 expression in maternal- versus paternal-deletion Il18 heterozygous mice on C57 background
DiscussionPrevious data present evidence for epigenetic mechanisms by which parentsmay differentially influence gene expression in the brain of daughtersversus sons and provide insights into sexually dimorphic epigeneticpathways recently uncovered in the brain.The X chromosome is enriched for genes involved in brain function.Investigating the potential relations between maternal and paternalgene expression programs may shed light on brainfunction, evolution, and disease.