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The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins

During development, tissue-specific patterns of gene expression are established by transcription factors and then stably maintained via epigenetic mechanisms. Cancer cells often express genes that are inappropriate for that tissue or developmental stage. Here, we show that high activity levels of Yk...

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Autores principales: Bairzin, Joanna C. D., Emmons-Bell, Maya, Hariharan, Iswar K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725458/
https://www.ncbi.nlm.nih.gov/pubmed/33298454
http://dx.doi.org/10.1126/sciadv.abe8159
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author Bairzin, Joanna C. D.
Emmons-Bell, Maya
Hariharan, Iswar K.
author_facet Bairzin, Joanna C. D.
Emmons-Bell, Maya
Hariharan, Iswar K.
author_sort Bairzin, Joanna C. D.
collection PubMed
description During development, tissue-specific patterns of gene expression are established by transcription factors and then stably maintained via epigenetic mechanisms. Cancer cells often express genes that are inappropriate for that tissue or developmental stage. Here, we show that high activity levels of Yki, the Hippo pathway coactivator that causes overgrowth in Drosophila imaginal discs, can also disrupt cell fates by altering expression of selector genes like engrailed (en) and Ultrabithorax (Ubx). Posterior clones expressing activated Yki can down-regulate en and express an anterior selector gene, cubitus interruptus (ci). The microRNA bantam and the chromatin regulator Taranis both function downstream of Yki in promoting ci expression. The boundary between Yki-expressing posterior clones and surrounding wild-type cells acquires properties reminiscent of the anteroposterior compartment boundary; Hedgehog signaling pathway activation results in production of Dpp. Thus, at least in principle, heterotypic interactions between Yki-expressing cells and their neighbors could activate boundary-specific signaling mechanisms.
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spelling pubmed-77254582020-12-16 The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins Bairzin, Joanna C. D. Emmons-Bell, Maya Hariharan, Iswar K. Sci Adv Research Articles During development, tissue-specific patterns of gene expression are established by transcription factors and then stably maintained via epigenetic mechanisms. Cancer cells often express genes that are inappropriate for that tissue or developmental stage. Here, we show that high activity levels of Yki, the Hippo pathway coactivator that causes overgrowth in Drosophila imaginal discs, can also disrupt cell fates by altering expression of selector genes like engrailed (en) and Ultrabithorax (Ubx). Posterior clones expressing activated Yki can down-regulate en and express an anterior selector gene, cubitus interruptus (ci). The microRNA bantam and the chromatin regulator Taranis both function downstream of Yki in promoting ci expression. The boundary between Yki-expressing posterior clones and surrounding wild-type cells acquires properties reminiscent of the anteroposterior compartment boundary; Hedgehog signaling pathway activation results in production of Dpp. Thus, at least in principle, heterotypic interactions between Yki-expressing cells and their neighbors could activate boundary-specific signaling mechanisms. American Association for the Advancement of Science 2020-12-09 /pmc/articles/PMC7725458/ /pubmed/33298454 http://dx.doi.org/10.1126/sciadv.abe8159 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Bairzin, Joanna C. D.
Emmons-Bell, Maya
Hariharan, Iswar K.
The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
title The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
title_full The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
title_fullStr The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
title_full_unstemmed The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
title_short The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
title_sort hippo pathway coactivator yorkie can reprogram cell fates and create compartment-boundary–like interactions at clone margins
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725458/
https://www.ncbi.nlm.nih.gov/pubmed/33298454
http://dx.doi.org/10.1126/sciadv.abe8159
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