2022
DOI: 10.1016/j.cell.2022.09.006
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Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes

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Cited by 33 publications
(23 citation statements)
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“…To change Fgf9 activity, a chromosomal rearrangement, affecting the distal part of the Fgf9 TAD, occurred in moles. Given TADs role in insulating a regulatory pattern, they ensure an integration of a newly established gene or a change in regulation to occur without huge alterations in neighborhood 64 . Thus, the regulatory context provided by TADs is an important object for the evolution of organisms.…”
Section: Discussionmentioning
confidence: 99%
“…To change Fgf9 activity, a chromosomal rearrangement, affecting the distal part of the Fgf9 TAD, occurred in moles. Given TADs role in insulating a regulatory pattern, they ensure an integration of a newly established gene or a change in regulation to occur without huge alterations in neighborhood 64 . Thus, the regulatory context provided by TADs is an important object for the evolution of organisms.…”
Section: Discussionmentioning
confidence: 99%
“…However, intrinsic E-P compatibility appears to play a lesser role in mammals where most enhancers activate all promoters by similar amounts (Bergman et al 2022;Martinez-Ara et al 2022;Zabidi et al 2014). Another potential mechanism for achieving divergent gene expression patterns within the same TAD could be promoter repression via CpG methylation, as was recently shown in the mouse Rex1/Fat1 locus (Ringel et al 2022). Our analysis of remote E-P interactions shows that promoters of skipped genes are often inactive, methylated, and inaccessible (Fig.…”
Section: Discussionmentioning
confidence: 98%
“…How is this E-P selectivity achieved in mammalian genomes? A recent study on a single mouse Rex1/Fat1 locus suggests that promoter repression through DNA methylation may result in an intra-TAD E-P specificity (Ringel et al 2022). To test if this mechanism is 5 generally utilized at other developmental loci, we systematically assessed the chromatin state of skipped promoters.…”
Section: Long-range Enhancer-promoter Specificity Is Linked To Repres...mentioning
confidence: 99%
“…Specifically, the depletion of cohesin subtly reduces enhancer–promoter contacts and leads to a small decrease in gene expression, but CTCF depletion can induce rewiring of interactions and ectopic gene activation in some cases, instead of generally reducing interactions between certain enhancers and promoters [70] . Furthermore, a recent study showed that a TAD physically separates Zfp42 and Fat1 , which have distinct local enhancers that drive their independent expression in ESCs (embryonic stem cells), but this separation is driven by chromatin activity independent of CTCF/cohesion [71] .…”
Section: Topological Insulators and Chromatin Mediators As A Function...mentioning
confidence: 99%