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Bacterial Artificial Chromosomes Establish Replication Timing And Sub-nuclear Compartment De Novo As Extra-chromosomal Vectors

Title: Bacterial Artificial Chromosomes Establish Replication Timing And Sub-nuclear Compartment De Novo As Extra-chromosomal Vectors.
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Name(s): Sima, Jiao, author
Bartlett, Daniel A., author
Gordon, Molly R., author
Gilbert, David M., author
Type of Resource: text
Genre: Journal Article
Text
Journal Article
Date Issued: 2018-02-28
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system (E-BACs) consisting of similar to 200 kb human bacterial artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) stable segregation elements. E-BACs were stably maintained as autonomous mini-chromosomes in EBNA1-expressing HeLa or human induced pluripotent stem cells (hiP-SCs) and established distinct RT patterns. An E-BAC harboring an early replicating chromosomal region replicated early during S phase, while E-BACs derived from RT transition regions (TTRs) and late replicating regions replicated in mid to late S phase. Analysis of E-BAC interactions with cellular chromatin (4C-seq) revealed that the early replicating E-BAC interacted broadly throughout the genome and preferentially with the early replicating compartment of the nucleus. In contrast, mid-to late-replicating E-BACs interacted with more specific late replicating chromosomal segments, some of which were shared between different E-BACs. Together, we describe a versatile system in which to study the structure and function of chromosomal segments that are stably maintained separately from the influence of cellular chromosome context.
Identifier: FSU_libsubv1_wos_000426293300025 (IID), 10.1093/nar/gkx1265 (DOI)
Keywords: origin, dna-replication, topologically associating domains, chromatin interactions, epstein-barr-virus, acute lymphoblastic-leukemia, beta-globin, latently infected-cells, stable replication, viral genomes
Publication Note: The publisher's version of record is available at https://doi.org/10.1093/nar/gkx1265
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000426293300025
Owner Institution: FSU
Is Part Of: Nucleic Acids Research.
0305-1048
Issue: iss. 4, vol. 46

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Sima, J., Bartlett, D. A., Gordon, M. R., & Gilbert, D. M. (2018). Bacterial Artificial Chromosomes Establish Replication Timing And Sub-nuclear Compartment De Novo As Extra-chromosomal Vectors. Nucleic Acids Research. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_wos_000426293300025