Human Artificial Chromosomes that Bypass Centromeric DNA.
HAC
centromere
chromatin
epigenetics
histone
human artificial chromosome
kinetochore
mitosis
nucleosome
synthetic chromosome
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 07 2019
25 07 2019
Historique:
received:
19
10
2018
revised:
07
04
2019
accepted:
03
06
2019
entrez:
27
7
2019
pubmed:
28
7
2019
medline:
28
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31348889
pii: S0092-8674(19)30634-8
doi: 10.1016/j.cell.2019.06.006
pmc: PMC6657561
pii:
doi:
Substances chimiques
Centromere Protein A
0
Centromere Protein B
0
DNA, Satellite
0
Nucleosomes
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
624-639.e19Subventions
Organisme : Wellcome Trust
ID : 092076
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203149
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R35 GM130302
Pays : United States
Organisme : Wellcome Trust
ID : 103897/Z/14
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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