Paper on E. coli DNA cytosine methylation in Nature Communications

Our paper on cytosine methylation in E. coli has been accepted for publication in Nature Communications. The work was started during Aswin's last few months in Cambridge, and was led by Christina Kahramanoglou (then at the Department of Pathology, Cambridge and now at the National Institute of Medical Research, London). Supriya in the lab here was a great help and was ably supported by Ankur, a project student. Congratulations and thanks to the entire team.

To quote from the paper abstract: 

DNA cytosine methylation regulates gene expression in mammals. In bacteria, its role in gene expression and genome architecture is less understood. Here, we perform high-throughput sequencing of bisulfite-treated genomic DNA from Escherichia coli K12 to describe, for the first time, the extent of cytosine methylation of bacterial DNA. Whereas most target sites (CmCWGG) are fully methylated in stationary phase cells, many sites with an extended CCmCWGG motif are only partially methylated in exponentially growing cells. We speculate that these partially methylated sites may be selected, as these are slightly correlated with the risk of spontaneous, non-synonymous conversion of methylated cytosines to thymines. Microarray analysis in a cytosine methylation-deficient mutant of E. coli shows increased expression of the stress response sigma factor RpoS and many of its targets in stationary phase. Thus, DNA cytosine methylation is a regulator of stationary phase gene expression in E. coli.

The paper is currently in press. We will place a link here as soon as it becomes available.

In Plain English for the busy:

DNA - a complex structure - consists of four building blocks

Specific modifications occur some of these blocks; 'methylation' of a block called 'cytosine' is one such example

Modifying a building block chemically alters the mechanical properties of the DNA srtucture, as well as how other objects interact with it

Methylated cytosine can convert to a different building block called thymine, thus causing a mutation, which may be good or bad

In mammals, methylation of cytosine plays important roles in describing how information in the DNA is read: this has implications on important processes including cancer

Our work - 

- shows that methylation of cytosine may have an effect on how information in the DNA is read by E. coli during 'stationary phase', a complex state of starvation and other stresses in which population growth is minimal

- suggests that how much of a cytosine is methylated may depend (to a small extent) on the risk of a bad mutation at this site 

We are funded by NCBS (DAE), DST, CSIR, DBT. and UGC