Integrative analysis of methylome and transcriptome reveals the importance of unmethylated CpGs in non-CpG island gene activation.
BACKGROUND
Promoter methylation is associated with gene repression; however, little is known about its mechanism. It was proposed that the repression of methylated genes is achieved through the recruitment of methyl binding proteins (MBPs) that participate in closing the chromatin. An alternative mechanism suggests that methylation interferes with the binding of either site specific activators or more general activators that bind to the CpG dinucleotide. However, the relative contribution of these two mechanisms to gene repression is not known.


RESULTS
Bioinformatics analyses of genome-wide transcriptome and methylome data support the latter hypothesis by demonstrating a strong association between transcription and the number of unmethylated CpGs at the promoter of genes lacking CpG islands.


CONCLUSIONS
Our results suggest that methylation represses gene expression mainly by preventing the binding of CpG binding activators.
Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel.
Amichai
A
Marx
Tamar
T
Kahan
Itamar
I
Simon
D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D059467:Transcriptome / Q000235:genetics*
D004268:DNA-Binding Proteins