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The Cooperation of Condensin, Histone Methylation, and Nuclear Lamina Tethering Maintains X Chromosome Repression After the Establishment of Dosage Compensation
The Cooperation of Condensin, Histone Methylation, and Nuclear Lamina Tethering Maintains X Chromosome Repression After the Establishment of Dosage Compensation
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152107
- ISBN
- 9798382741352
- DDC
- 574
- 서명/저자
- The Cooperation of Condensin, Histone Methylation, and Nuclear Lamina Tethering Maintains X Chromosome Repression After the Establishment of Dosage Compensation
- 발행사항
- [Sl] : University of Michigan, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 131 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Csankovszki, Gyorgyi.
- 학위논문주기
- Thesis (Ph.D.)--University of Michigan, 2024.
- 초록/해제
- 요약Caenorhabditis elegans exists as two heterogametic sexes: hermaphrodites and males. The hermaphrodites have two X chromosomes, XX, whereas the males only have one sex chromosome, XO. Without intervening processes during embryogenesis, the expression of hermaphrodite X would be twice that of males, resulting in XX lethality. Dosage compensation is the process that equalizes the expression of genes on the X chromosome between the sexes.The dosage compensation complex (DCC) binds to both X chromosomes of hermaphrodites during embryogenesis to reduce X gene expression levels to those observed in males. The DCC comprises a group of ten proteins, including the structural maintenance of the chromosome (SMC) protein-containing complex condensin IDC (dosage compensation) and five accessory proteins. Of particular interest is the non-condensin DCC member, DPY-21. When the DCC binds to the X chromosomes, it enriches monomethylation of histone 4 lysine 20 (H4K20me1) on the X chromosomes. In addition, the DCC cooperates with the nuclear lamina protein CEC-4 to tether the X to the nuclear periphery. All these events are necessary to maintain X-linked gene repression.Past studies have demonstrated that these mechanisms significantly impact gene expression and the structure of the X chromosome. It is also known that condensin IDC is required to establish dosage compensation during embryogenesis. Still, it is unclear whether condensin IDC is necessary for maintaining dosage compensation in mature C. elegans or if the additional mechanisms of H4K20me1 and nuclear lamina tethering can maintain repression without condensin IDC. Null mutations of the DCC subunits can cause varying degrees of lethality in hermaphrodites. However, hermaphrodites with mutations in the H4K20me1 and nuclear lamina tethering mechanisms are viable.In this dissertation, we conducted a study to assess whether combining mutations in all three known pathways would increase dosage compensation defects and destabilize repression during the maintenance phase of dosage compensation. To assess the function of DPY-27 during the maintenance period of dosage compensation, we used the auxin-inducible degron system to control its temporal depletion precisely. In addition to DPY-27, we incorporated loss-of-function mutations in cec-4 and dpy-21. Altogether, the depletion of all these pathways removes all known dosage compensation mechanisms. We uncovered that these mechanisms are essential for survival during the embryonic stages of development. However, larval stage and adult hermaphrodite C. elegans are capable of survival in the absence of all the dosage compensation processes described despite substantial increases in X-linked gene expression during the dosage compensation maintenance phase.
- 일반주제명
- Biology
- 일반주제명
- Molecular biology
- 일반주제명
- Genetics
- 일반주제명
- Cellular biology
- 일반주제명
- Developmental biology
- 키워드
- Gene regulation
- 키워드
- Chromosomes
- 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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■1001 ▼aTrombley, Jessica.
■24510▼aThe Cooperation of Condensin, Histone Methylation, and Nuclear Lamina Tethering Maintains X Chromosome Repression After the Establishment of Dosage Compensation
■260 ▼a[Sl]▼bUniversity of Michigan▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a131 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Csankovszki, Gyorgyi.
■5021 ▼aThesis (Ph.D.)--University of Michigan, 2024.
■520 ▼aCaenorhabditis elegans exists as two heterogametic sexes: hermaphrodites and males. The hermaphrodites have two X chromosomes, XX, whereas the males only have one sex chromosome, XO. Without intervening processes during embryogenesis, the expression of hermaphrodite X would be twice that of males, resulting in XX lethality. Dosage compensation is the process that equalizes the expression of genes on the X chromosome between the sexes.The dosage compensation complex (DCC) binds to both X chromosomes of hermaphrodites during embryogenesis to reduce X gene expression levels to those observed in males. The DCC comprises a group of ten proteins, including the structural maintenance of the chromosome (SMC) protein-containing complex condensin IDC (dosage compensation) and five accessory proteins. Of particular interest is the non-condensin DCC member, DPY-21. When the DCC binds to the X chromosomes, it enriches monomethylation of histone 4 lysine 20 (H4K20me1) on the X chromosomes. In addition, the DCC cooperates with the nuclear lamina protein CEC-4 to tether the X to the nuclear periphery. All these events are necessary to maintain X-linked gene repression.Past studies have demonstrated that these mechanisms significantly impact gene expression and the structure of the X chromosome. It is also known that condensin IDC is required to establish dosage compensation during embryogenesis. Still, it is unclear whether condensin IDC is necessary for maintaining dosage compensation in mature C. elegans or if the additional mechanisms of H4K20me1 and nuclear lamina tethering can maintain repression without condensin IDC. Null mutations of the DCC subunits can cause varying degrees of lethality in hermaphrodites. However, hermaphrodites with mutations in the H4K20me1 and nuclear lamina tethering mechanisms are viable.In this dissertation, we conducted a study to assess whether combining mutations in all three known pathways would increase dosage compensation defects and destabilize repression during the maintenance phase of dosage compensation. To assess the function of DPY-27 during the maintenance period of dosage compensation, we used the auxin-inducible degron system to control its temporal depletion precisely. In addition to DPY-27, we incorporated loss-of-function mutations in cec-4 and dpy-21. Altogether, the depletion of all these pathways removes all known dosage compensation mechanisms. We uncovered that these mechanisms are essential for survival during the embryonic stages of development. However, larval stage and adult hermaphrodite C. elegans are capable of survival in the absence of all the dosage compensation processes described despite substantial increases in X-linked gene expression during the dosage compensation maintenance phase.
■590 ▼aSchool code: 0127.
■650 4▼aBiology
■650 4▼aMolecular biology
■650 4▼aGenetics
■650 4▼aCellular biology
■650 4▼aDevelopmental biology
■653 ▼aGene regulation
■653 ▼aDosage compensation
■653 ▼aCaenorhabditis elegans
■653 ▼aChromosomes
■690 ▼a0307
■690 ▼a0306
■690 ▼a0369
■690 ▼a0379
■690 ▼a0758
■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=T17162877▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
