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Share Sequential onset and concurrent expression of miR-9 genomic loci in single cells contributes to the temporal increase of mature miR-9 in zebrafish neurogenesis
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Sequential onset and concurrent expression of miR-9 genomic loci in single cells contributes to the temporal increase of mature miR-9 in zebrafish neurogenesis
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.03.233890v1?rss=1
Authors: Soto, X., Minchington, T., Lea, R., Lee, J., Papalopulu, N.
Abstract:
Gene expression oscillations of the Hes/Her family members of transcriptional repressors are important for cell state transitions during neural development. The input of miR-9 is necessary to constrain gene expression noise, allowing oscillations to occur and to be decoded by downstream genes. Hes/Her dynamics are sensitive to the amount of miR-9 present in the cell but the mechanism by which miR-9 is quantitatively controlled is not known. In vertebrates, there are several distinct genomic loci that produce the same mature miR-9, leading to a number of possibilities of how the production of mature miR-9 may be regulated. Here, we show that the expression of miR-9 increases spatially and temporarily over zebrafish development. A detailed time course of the expression of 7 pri-miR-9 genomic loci shows that they have distinct temporal and spatial profiles, which may be brought about by different numbers of E/N-boxes in their regulatory regions. Focusing on pairs that are expressed in the same area of the hindbrain region, namely pri-miR-9-1/pri-miR-9-4 and pri-miR-9-1/pri-miR-9-5, we find that they sequentially activated during neurogenesis, concurrent with a known change in Her6 dynamics from noisy to oscillatory. Analysis of expression at the single-cell level shows that although they are sequentially activated, early and late pri-miRs are mostly concurrently transcriptionally active in the same cells. This finding supports the idea that increased mature miR-9 is contributed, at least in part, by overlapping activation of distinct loci. We propose that this may lead to an additive, sharp, increase of mature miR-9 which in turn may lead to rapid changes in Her6 dynamics.
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.03.233890v1?rss=1
Authors: Soto, X., Minchington, T., Lea, R., Lee, J., Papalopulu, N.
Abstract:
Gene expression oscillations of the Hes/Her family members of transcriptional repressors are important for cell state transitions during neural development. The input of miR-9 is necessary to constrain gene expression noise, allowing oscillations to occur and to be decoded by downstream genes. Hes/Her dynamics are sensitive to the amount of miR-9 present in the cell but the mechanism by which miR-9 is quantitatively controlled is not known. In vertebrates, there are several distinct genomic loci that produce the same mature miR-9, leading to a number of possibilities of how the production of mature miR-9 may be regulated. Here, we show that the expression of miR-9 increases spatially and temporarily over zebrafish development. A detailed time course of the expression of 7 pri-miR-9 genomic loci shows that they have distinct temporal and spatial profiles, which may be brought about by different numbers of E/N-boxes in their regulatory regions. Focusing on pairs that are expressed in the same area of the hindbrain region, namely pri-miR-9-1/pri-miR-9-4 and pri-miR-9-1/pri-miR-9-5, we find that they sequentially activated during neurogenesis, concurrent with a known change in Her6 dynamics from noisy to oscillatory. Analysis of expression at the single-cell level shows that although they are sequentially activated, early and late pri-miRs are mostly concurrently transcriptionally active in the same cells. This finding supports the idea that increased mature miR-9 is contributed, at least in part, by overlapping activation of distinct loci. We propose that this may lead to an additive, sharp, increase of mature miR-9 which in turn may lead to rapid changes in Her6 dynamics.
Copy rights belong to original authors. Visit the link for more info