Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • NEWS AND VIEWS

Two-layer design protects genes from mutations in their enhancers

Gene expression is regulated by clusters of regulatory DNA sequences called enhancers. Basic design principles that protect enhancer networks against the harmful effects of genetic mutations have now been elucidated.
  1. Ran Elkon

    1. Ran Elkon is in the Department of Human Genetics and Biochemistry, the Sackler Faculty of Medicine and the Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 6997801, Israel.

    View author publications

    You can also search for this author in PubMed  Google Scholar

  2. Reuven Agami

    1. Reuven Agami is at the Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.

    View author publications

    You can also search for this author in PubMed  Google Scholar

The human genome contains only about 20,000 protein-encoding genes1, yet gene expression is controlled by around one million regulatory DNA elements called enhancers2,3. Thus, each gene is regulated by multiple enhancers that collectively dictate the specific conditions — such as the cell types and developmental stages — in which it is expressed. Enhancers can be located a long distance away on the chromosome from the gene that they control (more than one million base pairs away). DNA looping brings the enhancers into close spatial proximity with a promoter sequence that lies immediately next to, and ultimately drives the expression of, their target genes. At present, how enhancers that are linked to the same gene cooperate is poorly understood. But, writing in Science, Lin et al.4 markedly advance our understanding of the architecture of such enhancer networks.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Nature 609, 477-478 (2022)

doi: https://doi.org/10.1038/d41586-022-02341-3

References

  1. Nurk, S. et al. Science 376, 44–53 (2022).

    Article  PubMed  Google Scholar 

  2. The ENCODE Project Consortium. Nature 489, 57–74 (2012).

    Article  PubMed  Google Scholar 

  3. Roadmap Epigenomics Consortium et al. Nature 518, 317–330 (2015).

    Article  PubMed  Google Scholar 

  4. Lin, X. et al. Science https://doi.org/10.1126/science.abk3512 (2022).

    Article  Google Scholar 

  5. Visscher, P. M. et al. Am. J. Hum. Genet. 101, 5–22 (2017).

    Article  PubMed  Google Scholar 

  6. Maurano, M. T. et al. Science 337, 1190–1195 (2012).

    Article  PubMed  Google Scholar 

  7. French, J. D. & Edwards, S. L. Trends Genet. 36, 880–891 (2020).

    Article  PubMed  Google Scholar 

  8. Korkmaz, G. et al. Nature Biotechnol. 34, 192–198 (2016).

    Article  PubMed  Google Scholar 

  9. Fulco, C. P. et al. Science 354, 769–773 (2016).

    Article  PubMed  Google Scholar 

  10. Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K. & Sharp, P. A. Cell 169, 13–23 (2017).

    Article  PubMed  Google Scholar 

  11. Sabari, B. R. et al. Science 361, eaar3958 (2018).

    Article  PubMed  Google Scholar 

  12. Torkamani, A., Wineinger, N. E. & Topol, E. J. Nature Rev. Genet. 19, 581–590 (2018).

    Article  PubMed  Google Scholar 

Download references

Competing Interests

The authors declare no competing interests.

Subjects

Latest on:

Nature Careers

Jobs

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing

Search

Advanced search

Quick links