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Dissecting the Regulators of DNA Replication Timing.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	Dissecting the Regulators of DNA Replication Timing./
作者:	Vouzas, Athanasios.
面頁冊數:	1 online resource (107 pages)
附註:	Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
Contained By:	Dissertations Abstracts International85-03B.
標題:	Molecular biology. -
電子資源:	click for full text (PQDT)
ISBN:	9798380415484

Dissecting the Regulators of DNA Replication Timing.
Vouzas, Athanasios.

Dissecting the Regulators of DNA Replication Timing. - 1 online resource (107 pages)

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

Thesis (Ph.D.)--The Florida State University, 2023.

Includes bibliographical references

During S-phase, the mammalian genome replicates in a defined temporal order called the DNA Replication Timing (RT) program. This program is developmentally regulated and is perturbed in diseased cell states, such as cancers and progeria. In recent years, the field has uncovered multiple layers of regulation of the RT program. These layers of regulation range from genome wide (Rif1), to chromosome wide (ASARs) and domain wide (ERCEs). Transcription is a process in the nucleus that tightly correlates with RT and has been suggested to be yet another way the cell regulates its RT program. Here I used a systematic approach to investigate how ectopic insertions of a series of transcription units in a late replicating domain influences the RT of that domain. Through this work, I show that transcription of a small gene is not sufficient to induce a RT advance. Since the only difference between the transcription units used in this study is the promoter itself, I posit that the local epigenetic environment built around the inserted promoter is critical for the ability of the promoter to induce a RT advance. Additionally, I present evidence that transcriptional activation using an inducible promoter can lead to a controlled RT advance. We also identified and characterized chromosome wide regulators of DNA RT, Asynchronous Replication and Autosomal RNAs (ASARs), across human autosomes. Utilizing the known features of ASARs, we identified 68 transcribed loci across human autosomes as candidate ARARs with allelic expression imbalance and asynchronous RT. Indeed, we discovered that five of these 68 transcribed loci share the characteristics and functionality of ASARs and classified them as novel ASARs. We further decoupled the RT of any particular ASAR allele from the RTs of the other allele, other ASARs on the same chromosome, and RT genome wide. Importantly, we showed that the RT of an ASAR allele was independent of the expression profile of the allele, which indicates that transcription is neither necessary nor sufficient to induce early DNA replication of the ASAR.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798380415484Subjects--Topical Terms:

583443
Molecular biology.
Subjects--Index Terms:

Asynchronous Replication and Autosomal RNAsIndex Terms--Genre/Form:

554714
Electronic books.

Dissecting the Regulators of DNA Replication Timing.
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520 $a During S-phase, the mammalian genome replicates in a defined temporal order called the DNA Replication Timing (RT) program. This program is developmentally regulated and is perturbed in diseased cell states, such as cancers and progeria. In recent years, the field has uncovered multiple layers of regulation of the RT program. These layers of regulation range from genome wide (Rif1), to chromosome wide (ASARs) and domain wide (ERCEs). Transcription is a process in the nucleus that tightly correlates with RT and has been suggested to be yet another way the cell regulates its RT program. Here I used a systematic approach to investigate how ectopic insertions of a series of transcription units in a late replicating domain influences the RT of that domain. Through this work, I show that transcription of a small gene is not sufficient to induce a RT advance. Since the only difference between the transcription units used in this study is the promoter itself, I posit that the local epigenetic environment built around the inserted promoter is critical for the ability of the promoter to induce a RT advance. Additionally, I present evidence that transcriptional activation using an inducible promoter can lead to a controlled RT advance. We also identified and characterized chromosome wide regulators of DNA RT, Asynchronous Replication and Autosomal RNAs (ASARs), across human autosomes. Utilizing the known features of ASARs, we identified 68 transcribed loci across human autosomes as candidate ARARs with allelic expression imbalance and asynchronous RT. Indeed, we discovered that five of these 68 transcribed loci share the characteristics and functionality of ASARs and classified them as novel ASARs. We further decoupled the RT of any particular ASAR allele from the RTs of the other allele, other ASARs on the same chromosome, and RT genome wide. Importantly, we showed that the RT of an ASAR allele was independent of the expression profile of the allele, which indicates that transcription is neither necessary nor sufficient to induce early DNA replication of the ASAR.
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