Biochemists working at the University of California, San Diego, have developed a program that predicts the placement of chemical marks that control the activity of genes¹ based on sequences of DNA². They describe their analysis and report results from its application to human embryonic³ cells in a paper published in Nature Methods online September 21. "All of our cells have the same blueprint⁴, the same DNA, although they serve separate functions," said John Whitaker, lead author of the report. "Skin cells protect, nerve cells send signals, and these differences emerge because different subsets of genes are active or silent within particular kinds of cells."

 

These patterns of activity are controlled by modifications⁶ of the DNA that do not alter its sequence -- chemical tags that influence which genes are read and which are skipped within a particular cell.

 

By comparing sequences with and without epigenomic modification⁵, the researchers identified DNA patterns associated with the changes. They call this novel analysis pipeline⁷ Epigram and have made both the program and the DNA motifs⁸ they identified openly available to other scientists.

 

"The interplay between genetic⁹ and epigenomic regulation has only begun to be deciphered," said Wei Wang, professor of chemistry and biochemistry who directed the work. "This study revealed that there are specific DNA sequences that are recognized by DNA-binding proteins," which specify¹⁰ exactly where other enzymes¹¹ place epigenomic marks.

 

The epigenome guides the development of complex organisms from single fertilized¹² eggs. The researchers analyzed¹³ epigenomic patterns in human embryonic stem cells and four cell lineages derived¹⁴ from them to catalogue genetic elements that shape the epigenome during development.

 

Damage to the epigenome not only disrupts development, but can happen at any point in our lives and sometimes leads to illness. Identification of the DNA sequences that guide the placement of epigenomic could guide experimental analysis, the authors say. By editing DNA sequences that control epigenomic modifications, scientists could probe their functions and perhaps in the future mend epigenomic mistakes that cause harm.

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