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Human Artificial Chromosomes that Bypass Centromeric DNA

Recent breakthroughs with synthetic budding yeast chromosomes expedite the creation of synthetic mammalian chromosomes and genomes. Mammals, unlike budding yeast, depend on the histone H3 variant, CENP-A, to epigenetically specify the location of the centromere—the locus essential for chromosome seg...

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Autores principales: Logsdon, Glennis A., Gambogi, Craig W., Liskovykh, Mikhail A., Barrey, Evelyne J., Larionov, Vladimir, Miga, Karen H., Heun, Patrick, Black, Ben E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657561/
https://www.ncbi.nlm.nih.gov/pubmed/31348889
http://dx.doi.org/10.1016/j.cell.2019.06.006
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author Logsdon, Glennis A.
Gambogi, Craig W.
Liskovykh, Mikhail A.
Barrey, Evelyne J.
Larionov, Vladimir
Miga, Karen H.
Heun, Patrick
Black, Ben E.
author_facet Logsdon, Glennis A.
Gambogi, Craig W.
Liskovykh, Mikhail A.
Barrey, Evelyne J.
Larionov, Vladimir
Miga, Karen H.
Heun, Patrick
Black, Ben E.
author_sort Logsdon, Glennis A.
collection PubMed
description Recent breakthroughs with synthetic budding yeast chromosomes expedite the creation of synthetic mammalian chromosomes and genomes. Mammals, unlike budding yeast, depend on the histone H3 variant, CENP-A, to epigenetically specify the location of the centromere—the locus essential for chromosome segregation. Prior human artificial chromosomes (HACs) required large arrays of centromeric α-satellite repeats harboring binding sites for the DNA sequence-specific binding protein, CENP-B. We report the development of a type of HAC that functions independently of these constraints. Formed by an initial CENP-A nucleosome seeding strategy, a construct lacking repetitive centromeric DNA formed several self-sufficient HACs that showed no uptake of genomic DNA. In contrast to traditional α-satellite HAC formation, the non-repetitive construct can form functional HACs without CENP-B or initial CENP-A nucleosome seeding, revealing distinct paths to centromere formation for different DNA sequence types. Our developments streamline the construction and characterization of HACs to facilitate mammalian synthetic genome efforts.
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spelling pubmed-66575612019-08-06 Human Artificial Chromosomes that Bypass Centromeric DNA Logsdon, Glennis A. Gambogi, Craig W. Liskovykh, Mikhail A. Barrey, Evelyne J. Larionov, Vladimir Miga, Karen H. Heun, Patrick Black, Ben E. Cell Article Recent breakthroughs with synthetic budding yeast chromosomes expedite the creation of synthetic mammalian chromosomes and genomes. Mammals, unlike budding yeast, depend on the histone H3 variant, CENP-A, to epigenetically specify the location of the centromere—the locus essential for chromosome segregation. Prior human artificial chromosomes (HACs) required large arrays of centromeric α-satellite repeats harboring binding sites for the DNA sequence-specific binding protein, CENP-B. We report the development of a type of HAC that functions independently of these constraints. Formed by an initial CENP-A nucleosome seeding strategy, a construct lacking repetitive centromeric DNA formed several self-sufficient HACs that showed no uptake of genomic DNA. In contrast to traditional α-satellite HAC formation, the non-repetitive construct can form functional HACs without CENP-B or initial CENP-A nucleosome seeding, revealing distinct paths to centromere formation for different DNA sequence types. Our developments streamline the construction and characterization of HACs to facilitate mammalian synthetic genome efforts. Cell Press 2019-07-25 /pmc/articles/PMC6657561/ /pubmed/31348889 http://dx.doi.org/10.1016/j.cell.2019.06.006 Text en © 2019 The Authors 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
Logsdon, Glennis A.
Gambogi, Craig W.
Liskovykh, Mikhail A.
Barrey, Evelyne J.
Larionov, Vladimir
Miga, Karen H.
Heun, Patrick
Black, Ben E.
Human Artificial Chromosomes that Bypass Centromeric DNA
title Human Artificial Chromosomes that Bypass Centromeric DNA
title_full Human Artificial Chromosomes that Bypass Centromeric DNA
title_fullStr Human Artificial Chromosomes that Bypass Centromeric DNA
title_full_unstemmed Human Artificial Chromosomes that Bypass Centromeric DNA
title_short Human Artificial Chromosomes that Bypass Centromeric DNA
title_sort human artificial chromosomes that bypass centromeric dna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657561/
https://www.ncbi.nlm.nih.gov/pubmed/31348889
http://dx.doi.org/10.1016/j.cell.2019.06.006
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