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EVOLUTIONARY GENETICS

A TAD refined for gene regulation

Nature Reviews Genetics volume 23, page 714 (2022)Cite this article

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An ongoing question in evolutionary biology is how genes arising in new locations — through mobilization or de novo origination — establish appropriate expression patterns without disrupting the regulation of nearby, pre-existing genes. Such considerations are particularly pertinent in topologically associating domains (TADs) of chromosomes, as genes within the same TAD have shared repertoires of available regulatory elements, which might limit opportunities for distinct regulatory programmes. A new study in Cell describes how local chromatin features enable differential regulation of genes within TADs.

To investigate potential mechanisms by which Fat1 and Zfp42 are independently regulated, the authors profiled the structure and chromatin features of the TAD both in mouse ESCs and in mouse embryonic day 11 limb buds. They identified that in ESCs, the TAD was subdivided into four separated subregions based on contact patterns, with Fat1 and Zfp42 located in different subregions, meaning that each gene is only contacting its local enhancers. Thus, even at the ESC stage when both genes are expressed, they are already subject to independent regulatory control. Perturbation experiments indicated that even though CTCF and cohesin are largely responsible for creating whole TADs, they were dispensable for the subdomain structure. Instead, the subdomain structure in ESCs seems to be driven by local chromatin state, with the Zfp42 and Fat1 genes displaying histone marks of active chromatin, whereas the DNA between these loci harbours inactive chromatin.

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  1. Nature Reviews Genetics http://www.nature.com/nrg/

    Darren J. Burgess

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  1. Darren J. Burgess
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Correspondence to Darren J. Burgess.

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Burgess, D.J. A TAD refined for gene regulation. Nat Rev Genet 23, 714 (2022). https://doi.org/10.1038/s41576-022-00549-7

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