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Genomic Imprinting and Inheritance

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...

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Induction of Protein Deletion Through In Utero Electroporation to Define Deficits in Neuronal Migration in Transgenic Models

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Expression of mouse Dab2ip transcript variants and gene methylation during brain development.

Farimah Salami¹, Shuhong Qiao¹, Ramin Homayouni¹

¹Department of Biological Sciences, University of Memphis, Memphis, TN, United States.

|May 11, 2015

Summary

Mouse Dab2ip (DOC-2/DAB2 interacting protein) gene expression is regulated by DNA methylation during cerebellar development. Increased methylation of CpG85 correlates with increased PH-domain containing mDab2ip transcripts.

Keywords:

AIP1 Cerebellum Dab1 GTPase activating protein

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Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain

Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain

Published on: July 12, 2012

Area of Science:

Neuroscience
Developmental Biology
Molecular Biology

Background:

Dab2ip (DOC-2/DAB2 interacting protein) is a RasGAP protein with known roles in prostate cancer and brain development.
Previous studies highlight Dab2ip's involvement in dendrite development and neuronal migration.

Purpose of the Study:

To characterize the mouse Dab2ip (mDab2ip) gene locus.
To investigate DNA methylation and expression patterns of mDab2ip during cerebellar development.
To identify mDab2ip transcript variants and their regulation.

Main Methods:

Analysis of cDNA sequences and FANTOM5 CAGE data to identify gene structure and transcription start sites.
Characterization of mDab2ip transcript variants using sequence analysis.
Bisulfate DNA sequencing to assess DNA methylation levels at CpG islands.
Real-time PCR to quantify transcript variant proportions.

Main Results:

The mDab2ip gene locus spans over 172kb with 20 possible exons and five transcription start sites.
Three mDab2ip transcript variants were identified, differing in the inclusion of exons encoding a nuclear localization signal and part of a PH-domain.
CpG85, located on exon 5, showed increased methylation during cerebellar development.
Expression of PH-domain containing mDab2ip transcripts increased during cerebellar development, correlating with CpG85 methylation.

Conclusions:

Site-specific DNA methylation of the mDab2ip gene, particularly at CpG85, may regulate alternative splicing.
This epigenetic regulation influences the inclusion of exon 5, leading to transcript variants encoding a full pleckstrin homology (PH) domain.
These findings suggest a novel mechanism for controlling Dab2ip function during cerebellar development.