Article Synopsis
- cis-Regulatory communication is vital for mammalian development and is often limited by topologically associating domains (TADs) in the genome.
- The study found that the Linx promoter acts as a long-range silencer for the Xist locus, affecting which X chromosome is inactivated, regardless of Linx transcription and without impacting the nearby Tsix regulator.
- Interestingly, when LinxP is placed in the same TAD as Xist, it can change its role from a silencer to an enhancer, revealing new insights into the regulatory mechanisms of X chromosome inactivation.
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Article Abstract
cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964159 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2019.10.030 | DOI Listing |
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