In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-09-26)
Abstract:
The building blocks of DNA are four molecules commonly named ‘A’, ‘T’, ‘C’ and ‘G’. The order of these DNA letters in a gene contains the instructions to make specific proteins or other molecules. Other stretches of DNA contain codes that direct the cell's machinery to genes that need to be switched on or switched off. The start of a gene, for example, has a stretch of DNA called a promoter, which is where the molecular machinery that switches on the gene is assembled. A human cell can contain over two and half metres of DNA. To get this length to fit inside the cell, the DNA is wrapped tightly around proteins to form a structure called chromatin. However, this packing can make it difficult to access the right gene at the right time. As such, chromatin is often marked with small chemical tags that earmark which genes should be either activated or inactivated, and/or that cause the DNA to unpack. Most gene promoters contain a sequence of DNA with many Cs and Gs found one after the other, called a CpG island. Researchers have previously shown that the chromatin of CpG islands has two types of chemical markings—one that normally marks active genes, and another that often marks inactive genes. It was suggested that having both kinds of markings allows CpG islands to prime nearby genes, so that they are ready to be quickly switched on or off as the cell develops. However, the features of the DNA sequence in these CpG islands that are important for this process had not been directly tested. Wachter et al. have now inserted an artificial DNA sequence that included a CpG island into mouse stem cells. The chromatin around these CpG islands was readily marked with both activating and inactivating chemical marks. Furthermore, by changing the sequence of the artificial DNA, Wachter et al. revealed that these chemical marks were only added when the DNA sequences contained a lot of Cs followed by Gs. Other artificial sequences with lots of Cs and Gs, but where Gs were rarely found immediately after the Cs, had neither of the two chemical marks on the chromatin. This suggests that nearby genes would be harder to locate and activate as the cell grows and develops. On the other hand, when the DNA contained a lot of As and Ts, the chemical marks were added directly to the DNA (rather than to the chromatin)—and this prevented both the activating and the inactivating chemical marks being added to the chromatin. Now that the common features of CpG islands that influence chromatin are known, the next step is to find out how this is achieved. Further work will be needed to uncover which proteins in a cell interpret these DNA sequence such that nearby genes can be switched on or off.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.03397.001
DOI:
10.7554/eLife.03397.002
DOI:
10.7554/eLife.03397.003
DOI:
10.7554/eLife.03397.004
DOI:
10.7554/eLife.03397.005
DOI:
10.7554/eLife.03397.006
DOI:
10.7554/eLife.03397.007
DOI:
10.7554/eLife.03397.008
DOI:
10.7554/eLife.03397.009
DOI:
10.7554/eLife.03397.010
DOI:
10.7554/eLife.03397.011
DOI:
10.7554/eLife.03397.012
DOI:
10.7554/eLife.03397.013
DOI:
10.7554/eLife.03397.014
DOI:
10.7554/eLife.03397.015
DOI:
10.7554/eLife.03397.016
DOI:
10.7554/eLife.03397.017
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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