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Mapping higher order structure of chromatin domains

Nature Genetics volume 43, pages 615–616 (2011)Cite this article

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Large-scale mapping of chromatin state and transcription factor binding have uncovered many broad chromatin domains along linear genomic DNA, but it is unclear how these functional domains are organized in three-dimensional nuclear space. A new study now shows that many domains exist as loops connected by CCTC-binding factor (CTCF), providing new insights into the higher-order structure of chromatin organization in the nucleus.

In eukaryotic cells, linear DNA is packaged into a highly compact chromatin structure that undergoes dynamic changes at different phases of the cell cycle and in response to various intracellular and extracellular signals. In turn, chromatin organization can have a fundamental impact on various nuclear processes including transcription, DNA replication and repair1. Recent advances in genomic technologies have led to the identification of a large number of chromatin domains in the mammalian genome, showing that the eukaryotic genome is highly compartmentalized, with functionally distinct segments interspersed and intertwined2. For example, a large fraction of the genome, known as LADs, for lamina associated domains, is associated with the nuclear membrane and correlates with low transcriptional activity3. Other genomic domains have been found to be enriched for the chromatin modification H3K27Me3, a mark associated with transcriptional silencing that can expand during the differentiation of pluripotent cells to various lineages4. However, despite the rapidly increasing list of chromatin domains being identified, little is actually known about their higher order structure. On page 630 of this issue, Chia-Lin Wei and colleagues5 use a new genomic technology that combines chromatin immunoprecipitation (ChIP), 3C and high throughput sequencing to reveal the three-dimensional organization of many of the chromatin domains in murine embryonic stem cells (mES).

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Figure 1: Five distinct chromatin domains are found in association with CTCF in mouse embryonic stem cells.

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  1. Celso A. Espinoza and Bing Ren are at the Ludwig Institute for Cancer Research at the University of California, San Diego, La Jolla, California, USA.,

    Celso A Espinoza & Bing Ren

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  1. Celso A Espinoza
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  2. Bing Ren
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Correspondence to Bing Ren.

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Espinoza, C., Ren, B. Mapping higher order structure of chromatin domains. Nat Genet 43, 615–616 (2011). https://doi.org/10.1038/ng.869

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