Yin et al., Science, 2017

The DNA letter C exists in two forms, cytosine and methylcytosine, which can be thought of as the same letter with and without an accent (C and Ç). Methylation of DNA bases is a type of epigenetic modification, a biochemical change in the genome that doesn’t alter the DNA sequence. The two variants of C have no effect on the kind of proteins that can be made, but they can have a major influence on when and where the proteins are produced. Previous research has shown that genomic regions where C is methylated are commonly inactive and that many transcription factors are unable to bind to sequences that contain the methylated Ç.

By analysing hundreds of different human transcription factors, Taipale lab has found that certain transcription factors actually prefer the methylated Ç. These include transcription factors that are important in embryonic development, and for the development of prostate and colorectal cancers.

“The results suggest that such ‘master’ regulatory factors could activate regions of the genome that are normally inactive, leading to the formation of organs during development, or the initiation of pathological changes in cells that lead to diseases such as cancer”, says Professor Jussi Taipale.

The results pave the way for cracking the genetic code that controls the expression of genes, and will have broad implications in the understanding of development and disease, since the availability of genomic information relevant to disease is expanding at an exponentially increasing rate.

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