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Mechanistic Insights Into Chromatin Modulation by MacroH2A and ADP-Ribosylation
Mechanistic Insights Into Chromatin Modulation by MacroH2A and ADP-Ribosylation
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202105138
- ISBN
- 9798293894963
- DDC
- 540
- 저자명
- Huang, Yingzi.
- 서명/저자
- Mechanistic Insights Into Chromatin Modulation by MacroH2A and ADP-Ribosylation
- 발행사항
- [Sl] : Princeton University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 214 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-04, Section: B.
- 주기사항
- Advisor: Muir, Tom W.
- 학위논문주기
- Thesis (Ph.D.)--Princeton University, 2025.
- 초록/해제
- 요약Eukaryotic gene expression can be regulated through changes in chromatin composition, including the deposition of histone variants and the installation of diverse post-translational modifications on histones. Exploring how these chromatin features influence molecular mechanisms directly or through their effects on other nuclear factors is essential for understanding how transcription is regulated and genome stability is preserved. This thesis seeks to address these questions through three complementary approaches: biochemical reconstitution of defined chromatin substrates, chemical biology strategies for installing site-specific modifications, and proteomics for mapping protein interactions.First, nucleosomes containing the histone variant macroH2A were prepared using recombinant and semi-synthetic strategies. MacroH2A formed heterotypic nucleosomes that altered chromatin folding, reduced remodeling activity, and showed selective interplay with heterochromatin associated Polycomb complexes.Second, photo-proximity labeling platforms were developed to map macroH2A interactors on native chromatin. Two complementary approaches were used: a genetically encoded system (LITag) and a synthetic flavin-based photocatalyst. The latter was developed as part of ongoing work in the Muir group. Together, these methods enabled the identification of macroH2A interactomes, revealing associations with chromatin remodeling factors and proteins involved in the DNA damage response.Third, a semi-synthetic system was established to install mono- and poly-ADPribosylation (ADPr) on histones in isolated nuclei. Photo-crosslinking proteomics identified direct histone ADPr-binding proteins, including helicases, chromatin kinases, and DNA repair factors. Together, these studies demonstrate how histone variants and post-translational modifications shape chromatin architecture and recruit effector proteins, and they provide modular tools for probing chromatin signaling.
- 일반주제명
- Chemistry
- 일반주제명
- Biochemistry
- 일반주제명
- Molecular biology
- 일반주제명
- Genetics
- 키워드
- Histone variants
- 기타저자
- Princeton University Chemistry
- 기본자료저록
- Dissertations Abstracts International. 87-04B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798293894963
■035 ▼a(MiAaPQ)AAI32240143
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a540
■1001 ▼aHuang, Yingzi.
■24510▼aMechanistic Insights Into Chromatin Modulation by MacroH2A and ADP-Ribosylation
■260 ▼a[Sl]▼bPrinceton University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a214 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-04, Section: B.
■500 ▼aAdvisor: Muir, Tom W.
■5021 ▼aThesis (Ph.D.)--Princeton University, 2025.
■520 ▼aEukaryotic gene expression can be regulated through changes in chromatin composition, including the deposition of histone variants and the installation of diverse post-translational modifications on histones. Exploring how these chromatin features influence molecular mechanisms directly or through their effects on other nuclear factors is essential for understanding how transcription is regulated and genome stability is preserved. This thesis seeks to address these questions through three complementary approaches: biochemical reconstitution of defined chromatin substrates, chemical biology strategies for installing site-specific modifications, and proteomics for mapping protein interactions.First, nucleosomes containing the histone variant macroH2A were prepared using recombinant and semi-synthetic strategies. MacroH2A formed heterotypic nucleosomes that altered chromatin folding, reduced remodeling activity, and showed selective interplay with heterochromatin associated Polycomb complexes.Second, photo-proximity labeling platforms were developed to map macroH2A interactors on native chromatin. Two complementary approaches were used: a genetically encoded system (LITag) and a synthetic flavin-based photocatalyst. The latter was developed as part of ongoing work in the Muir group. Together, these methods enabled the identification of macroH2A interactomes, revealing associations with chromatin remodeling factors and proteins involved in the DNA damage response.Third, a semi-synthetic system was established to install mono- and poly-ADPribosylation (ADPr) on histones in isolated nuclei. Photo-crosslinking proteomics identified direct histone ADPr-binding proteins, including helicases, chromatin kinases, and DNA repair factors. Together, these studies demonstrate how histone variants and post-translational modifications shape chromatin architecture and recruit effector proteins, and they provide modular tools for probing chromatin signaling.
■590 ▼aSchool code: 0181.
■650 4▼aChemistry
■650 4▼aBiochemistry
■650 4▼aMolecular biology
■650 4▼aGenetics
■653 ▼aHistone variants
■653 ▼aPost-translational modifications
■653 ▼aProximity labeling platforms
■653 ▼aChromatin composition
■690 ▼a0485
■690 ▼a0487
■690 ▼a0369
■690 ▼a0307
■71020▼aPrinceton University▼bChemistry.
■7730 ▼tDissertations Abstracts International▼g87-04B.
■790 ▼a0181
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17359562▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
