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Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes

Timely progression of a genetic program is critical for embryonic development. However, gene expression involves inevitable fluctuations in biochemical reactions leading to substantial cell-to-cell variability (gene expression noise). One of the important questions in developmental biology is how pa...

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Autores principales: Zinani, Oriana Q.H., Keseroğlu, Kemal, Dey, Supravat, Ay, Ahmet, Singh, Abhyudai, Özbudak, Ertuğrul M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250017/
https://www.ncbi.nlm.nih.gov/pubmed/35789861
http://dx.doi.org/10.1016/j.isci.2022.104579
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author Zinani, Oriana Q.H.
Keseroğlu, Kemal
Dey, Supravat
Ay, Ahmet
Singh, Abhyudai
Özbudak, Ertuğrul M.
author_facet Zinani, Oriana Q.H.
Keseroğlu, Kemal
Dey, Supravat
Ay, Ahmet
Singh, Abhyudai
Özbudak, Ertuğrul M.
author_sort Zinani, Oriana Q.H.
collection PubMed
description Timely progression of a genetic program is critical for embryonic development. However, gene expression involves inevitable fluctuations in biochemical reactions leading to substantial cell-to-cell variability (gene expression noise). One of the important questions in developmental biology is how pattern formation is reproducibly executed despite these unavoidable fluctuations in gene expression. Here, we studied the transcriptional variability of two paired zebrafish segmentation clock genes (her1 and her7) in multiple genetic backgrounds. Segmentation clock genes establish an oscillating self-regulatory system, presenting a challenging yet beautiful system in studying control of transcription variability. In this study, we found that a negative feedback loop established by the Her1 and Her7 proteins minimizes uncorrelated variability whereas gene copy number affects variability of both RNAs in a similar manner (correlated variability). We anticipate that these findings will help analyze the precision of other natural clocks and inspire the ideas for engineering precise synthetic clocks in tissue engineering.
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spelling pubmed-92500172022-07-03 Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes Zinani, Oriana Q.H. Keseroğlu, Kemal Dey, Supravat Ay, Ahmet Singh, Abhyudai Özbudak, Ertuğrul M. iScience Article Timely progression of a genetic program is critical for embryonic development. However, gene expression involves inevitable fluctuations in biochemical reactions leading to substantial cell-to-cell variability (gene expression noise). One of the important questions in developmental biology is how pattern formation is reproducibly executed despite these unavoidable fluctuations in gene expression. Here, we studied the transcriptional variability of two paired zebrafish segmentation clock genes (her1 and her7) in multiple genetic backgrounds. Segmentation clock genes establish an oscillating self-regulatory system, presenting a challenging yet beautiful system in studying control of transcription variability. In this study, we found that a negative feedback loop established by the Her1 and Her7 proteins minimizes uncorrelated variability whereas gene copy number affects variability of both RNAs in a similar manner (correlated variability). We anticipate that these findings will help analyze the precision of other natural clocks and inspire the ideas for engineering precise synthetic clocks in tissue engineering. Elsevier 2022-06-11 /pmc/articles/PMC9250017/ /pubmed/35789861 http://dx.doi.org/10.1016/j.isci.2022.104579 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zinani, Oriana Q.H.
Keseroğlu, Kemal
Dey, Supravat
Ay, Ahmet
Singh, Abhyudai
Özbudak, Ertuğrul M.
Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
title Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
title_full Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
title_fullStr Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
title_full_unstemmed Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
title_short Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
title_sort gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250017/
https://www.ncbi.nlm.nih.gov/pubmed/35789861
http://dx.doi.org/10.1016/j.isci.2022.104579
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