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Encoding Cell Cycle Regulatory Information in the Genome
Encoding Cell Cycle Regulatory Information in the Genome
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152052
- ISBN
- 9798382738345
- DDC
- 574
- 저자명
- Buchert, Elli M.
- 서명/저자
- Encoding Cell Cycle Regulatory Information in the Genome
- 발행사항
- [Sl] : University of Michigan, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 198 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Buttitta, Laura A.
- 학위논문주기
- Thesis (Ph.D.)--University of Michigan, 2024.
- 초록/해제
- 요약The timing of cell cycle exit and initiation of terminal differentiation must be precisely coordinated to ensure proper development of many tissues. Additional cell cycles during development can disrupt, but not necessarily prevent, progression of terminal differentiation programs, leading to tissues with incorrect cell numbers and morphology. The mechanisms that coordinate the transition from a proliferative state to a fully differentiated post-mitotic state are not well understood, and even less is understood about how a non-cycling postmitotic state is maintained in terminally differentiated cells. The eyes and wings of the fruit fly Drosophila melanogaster are excellent tissues to study this phenomenon, as both tissues undergo a relatively synchronous final cell cycle before exiting the cell cycle permanently at 24h after the start of metamorphosis, coincident with visible progression of terminal differentiation programs.Cell cycle exit in Drosophila wings and eyes involves the transcriptional silencing of hundreds of cell cycle genes. However, maintaining cell cycle exit relies on preventing the re-activation of three rate-limiting cell cycle genes, the G1-S cyclin, Cyclin E, the cell cycle transcriptional activator, E2F1 and the regulator of mitotic entry, cdc25c, termed String in flies. Our prior work established that after cell cycle exit, chromatin accessibility is reduced at potential regulatory elements for these three genes, leading to a hypothesis that closing chromatin maintains cell cycle exit by preventing activation of the rate-limiting cell cycle genes. In this thesis I examine this hypothesis by developing new techniques to allow for more detailed assays of chromatin accessibility changes and chromatin modifications (Chapter 2). I also test and validate several regulatory elements for the e2f1 and string loci, to determine which elements are tissue specific vs. shared for the wing and eye and examine their shut off dynamics during chromatin accessibility changes after cell cycle exit (Chapter 3). Finally, I identify a chromatin remodeler responsible for the closing of chromatin accessibility at the string locus, and determine that it works together with a transcription factor expressed during metamorphosis to coordinate chromatin accessibility changes that decommission enhancers at cell cycle genes and early differentiation genes, to maintain cell cycle exit as terminal differentiation progresses (Chapter 4). Altogether this work examines how complex cell cycle regulatory events can be encoded in the genome, to ensure the proper coordination of cell cycle control with cellular differentiation.
- 일반주제명
- Molecular biology
- 일반주제명
- Developmental biology
- 일반주제명
- Cellular biology
- 일반주제명
- Entomology
- 일반주제명
- Genetics
- 일반주제명
- Morphology
- 키워드
- Cell cycle
- 키워드
- Gene regulation
- 키워드
- Metamorphosis
- 기타저자
- University of Michigan Molecular Cellular and Developmental Biology
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211152052
■006m o d
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■020 ▼a9798382738345
■035 ▼a(MiAaPQ)AAI31348868
■035 ▼a(MiAaPQ)umichrackham005403
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aBuchert, Elli M.
■24510▼aEncoding Cell Cycle Regulatory Information in the Genome
■260 ▼a[Sl]▼bUniversity of Michigan▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a198 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Buttitta, Laura A.
■5021 ▼aThesis (Ph.D.)--University of Michigan, 2024.
■520 ▼aThe timing of cell cycle exit and initiation of terminal differentiation must be precisely coordinated to ensure proper development of many tissues. Additional cell cycles during development can disrupt, but not necessarily prevent, progression of terminal differentiation programs, leading to tissues with incorrect cell numbers and morphology. The mechanisms that coordinate the transition from a proliferative state to a fully differentiated post-mitotic state are not well understood, and even less is understood about how a non-cycling postmitotic state is maintained in terminally differentiated cells. The eyes and wings of the fruit fly Drosophila melanogaster are excellent tissues to study this phenomenon, as both tissues undergo a relatively synchronous final cell cycle before exiting the cell cycle permanently at 24h after the start of metamorphosis, coincident with visible progression of terminal differentiation programs.Cell cycle exit in Drosophila wings and eyes involves the transcriptional silencing of hundreds of cell cycle genes. However, maintaining cell cycle exit relies on preventing the re-activation of three rate-limiting cell cycle genes, the G1-S cyclin, Cyclin E, the cell cycle transcriptional activator, E2F1 and the regulator of mitotic entry, cdc25c, termed String in flies. Our prior work established that after cell cycle exit, chromatin accessibility is reduced at potential regulatory elements for these three genes, leading to a hypothesis that closing chromatin maintains cell cycle exit by preventing activation of the rate-limiting cell cycle genes. In this thesis I examine this hypothesis by developing new techniques to allow for more detailed assays of chromatin accessibility changes and chromatin modifications (Chapter 2). I also test and validate several regulatory elements for the e2f1 and string loci, to determine which elements are tissue specific vs. shared for the wing and eye and examine their shut off dynamics during chromatin accessibility changes after cell cycle exit (Chapter 3). Finally, I identify a chromatin remodeler responsible for the closing of chromatin accessibility at the string locus, and determine that it works together with a transcription factor expressed during metamorphosis to coordinate chromatin accessibility changes that decommission enhancers at cell cycle genes and early differentiation genes, to maintain cell cycle exit as terminal differentiation progresses (Chapter 4). Altogether this work examines how complex cell cycle regulatory events can be encoded in the genome, to ensure the proper coordination of cell cycle control with cellular differentiation.
■590 ▼aSchool code: 0127.
■650 4▼aMolecular biology
■650 4▼aDevelopmental biology
■650 4▼aCellular biology
■650 4▼aEntomology
■650 4▼aGenetics
■650 4▼aMorphology
■653 ▼aCell cycle
■653 ▼aChromatin accessibility
■653 ▼aGene regulation
■653 ▼aDrosophila melanogaster
■653 ▼aMetamorphosis
■690 ▼a0758
■690 ▼a0307
■690 ▼a0379
■690 ▼a0369
■690 ▼a0353
■690 ▼a0287
■71020▼aUniversity of Michigan▼bMolecular, Cellular, and Developmental Biology.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0127
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162766▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
