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We analyzed the DNA methylome of ten subpopulations spanning the entire B cell differentiation program by whole-genome bisulfite sequencing and high-density microarrays. We observed that non-CpG methylation disappeared upon B cell commitment, whereas CpG methylation changed extensively during B cell maturation, showing an accumulative pattern and affecting around 30% of all measured CpG sites. Early differentiation stages mainly displayed enhancer demethylation, which was associated with upregulation of key B cell transcription factors and affected multiple genes involved in B cell biology. Late differentiation stages, in contrast, showed extensive demethylation of heterochromatin and methylation gain at Polycomb-repressed areas, and genes with apparent functional impact in B cells were not affected. This signature, which has previously been linked to aging and cancer, was particularly widespread in mature cells with an extended lifespan. Comparing B cell neoplasms with their normal counterparts, we determined that they frequently acquire methylation changes in regions already undergoing dynamic methylation during normal B cell differentiation.

We apply a known algorithm for computing exactly inequalities between Beta distributions to assess whether a given position in a genome is differentially methylated across samples. We discuss the advantages brought by the adoption of this solution with respect to two approximations (Fisher's test and Z score). The same formalism presented here can be applied in a similar way to variant calling. [ABSTRACT FROM AUTHOR]

Sequencing DNA from several organisms has revealed that duplication and drift of existing genes have primarily moulded the contents of a given genome. Though the effect of knocking out or overexpressing a particular gene has been studied in many organisms, no study has systematically explored the effect of adding new links in a biological network. To explore network evolvability, we constructed 598 recombinations of promoters (including regulatory regions) with different transcription or σ-factor genes in Escherichia coli, added over a wild-type genetic background. Here we show that ∼95% of new networks are tolerated by the bacteria, that very few alter growth, and that expression level correlates with factor position in the wild-type network hierarchy. Most importantly, we find that certain networks consistently survive over the wild type under various selection pressures. Therefore new links in the network are rarely a barrier for evolution and can even confer a fitness advantage. [ABSTRACT FROM AUTHOR]