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Reconstituting Drosophila Centromere Identity in Human Cells
The centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, centromere protein (CENP)-A, yet how its self-propagation is achieved remains poorly understood. Here, we develop a hetero...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900781/ https://www.ncbi.nlm.nih.gov/pubmed/31597104 http://dx.doi.org/10.1016/j.celrep.2019.08.067 |
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author | Roure, Virginie Medina-Pritchard, Bethan Lazou, Vasiliki Rago, Luciano Anselm, Eduard Venegas, Daniela Jeyaprakash, A. Arockia Heun, Patrick |
author_facet | Roure, Virginie Medina-Pritchard, Bethan Lazou, Vasiliki Rago, Luciano Anselm, Eduard Venegas, Daniela Jeyaprakash, A. Arockia Heun, Patrick |
author_sort | Roure, Virginie |
collection | PubMed |
description | The centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, centromere protein (CENP)-A, yet how its self-propagation is achieved remains poorly understood. Here, we develop a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C, and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify CAL1 to be required for dCENP-C loading onto chromatin in cooperation with dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of Drosophila centromere identity. |
format | Online Article Text |
id | pubmed-6900781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-69007812020-01-21 Reconstituting Drosophila Centromere Identity in Human Cells Roure, Virginie Medina-Pritchard, Bethan Lazou, Vasiliki Rago, Luciano Anselm, Eduard Venegas, Daniela Jeyaprakash, A. Arockia Heun, Patrick Cell Rep Article The centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, centromere protein (CENP)-A, yet how its self-propagation is achieved remains poorly understood. Here, we develop a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C, and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify CAL1 to be required for dCENP-C loading onto chromatin in cooperation with dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of Drosophila centromere identity. Cell Press 2019-10-08 /pmc/articles/PMC6900781/ /pubmed/31597104 http://dx.doi.org/10.1016/j.celrep.2019.08.067 Text en Crown Copyright © 2019. http://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 Roure, Virginie Medina-Pritchard, Bethan Lazou, Vasiliki Rago, Luciano Anselm, Eduard Venegas, Daniela Jeyaprakash, A. Arockia Heun, Patrick Reconstituting Drosophila Centromere Identity in Human Cells |
title | Reconstituting Drosophila Centromere Identity in Human Cells |
title_full | Reconstituting Drosophila Centromere Identity in Human Cells |
title_fullStr | Reconstituting Drosophila Centromere Identity in Human Cells |
title_full_unstemmed | Reconstituting Drosophila Centromere Identity in Human Cells |
title_short | Reconstituting Drosophila Centromere Identity in Human Cells |
title_sort | reconstituting drosophila centromere identity in human cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900781/ https://www.ncbi.nlm.nih.gov/pubmed/31597104 http://dx.doi.org/10.1016/j.celrep.2019.08.067 |
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