Jan Korbel | PubMed Health

PubMed2004

Transgene methylation in mice reflects copy number but not expression level.

In mammals, CpG methylation is one of the mechanisms of epigenetic control over the linear sequence of bases of deoxyribonucleic acid (DNA); about 70% of CpG dinucleotides are methylated. The actual signal that triggers DNA methylation is not known, although repetitive DNA has been shown to be an attractive template for DNA methylases. To address methylation events associated with transgenic copy number, we have analyzed transgenes that are actively transcribed in a tissue-specific manner. We have compared gross transgene methylation by restriction-enzyme digestion in expressing and nonexpressing tissues. The observed pattern suggests that the DNA methylation machinery can recognize repeated genomic sequences independently of their transcriptional activity.

Animals↗

PubMed2001

Extracting information from cDNA arrays.

High-density DNA arrays allow measurements of gene expression levels (messenger RNA abundance) for thousands of genes simultaneously. We analyze arrays with spotted cDNA used in monitoring of expression profiles. A dilution series of a mouse liver probe is deployed to quantify the reproducibility of expression measurements. Saturation effects limit the accessible signal range at high intensities. Additive noise and outshining from neighboring spots dominate at low intensities. For repeated measurements on the same filter and filter-to-filter comparisons correlation coefficients of 0.98 are found. Next we consider the clustering of gene expression time series from stimulated human fibroblasts which aims at finding co-regulated genes. We analyze how preprocessing, the distance measure, and the clustering algorithm affect the resulting clusters. Finally we discuss algorithms for the identification of transcription factor binding sites from clusters of co-regulated genes. (c) 2001 American Institute of Physics.

Journal Article↗