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Resolving the Three-Dimensional Interactome of Human Accelerated Regions During Human and Chimpanzee Neurodevelopment
Resolving the Three-Dimensional Interactome of Human Accelerated Regions During Human and Chimpanzee Neurodevelopment
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103030
- ISBN
- 9798286441730
- DDC
- 575
- 저자명
- Pal, Atreyo.
- 서명/저자
- Resolving the Three-Dimensional Interactome of Human Accelerated Regions During Human and Chimpanzee Neurodevelopment
- 발행사항
- [Sl] : Yale University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 179 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Noonan, James P.
- 학위논문주기
- Thesis (Ph.D.)--Yale University, 2025.
- 초록/해제
- 요약Human Accelerated Regions (HARs) are regulatory elements highly conserved across species but exhibit a significant excess of human-specific sequence changes. They include transcriptional enhancers with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unclear whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. We generated a high-resolution map of chromatin interactions for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs) to comprehensively identify gene targets in both species. HARs and their chimpanzee orthologs targeted a conserved set of genes enriched for neurodevelopmental processes including neurogenesis and synaptic transmission. Changes in HAR enhancer activity were correlated with changes in conserved gene target expression. Conserved targets were enriched among genes differentially expressed between human and chimpanzee NSCs or between human and non-human primate brain. Species-specific HAR gene targets did not converge on known biological functions and were not significantly enriched among differentially expressed genes, suggesting that HARs did not alter gene expression via enhancer hijacking. HAR gene targets also showed cell type-specific expression patterns in the developing human brain, including outer radial glia, which are hypothesized to contribute to human cortical expansion. Our findings support that HARs influenced human brain evolution by altering the expression of conserved gene targets and provide the means to functionally link HARs with novel human brain features.
- 일반주제명
- Genetics
- 일반주제명
- Evolution & development
- 일반주제명
- Neurosciences
- 일반주제명
- Biology
- 기타저자
- Yale University Genetics
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■007cr#unu||||||||
■020 ▼a9798286441730
■035 ▼a(MiAaPQ)AAI31845777
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a575
■1001 ▼aPal, Atreyo.
■24510▼aResolving the Three-Dimensional Interactome of Human Accelerated Regions During Human and Chimpanzee Neurodevelopment
■260 ▼a[Sl]▼bYale University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a179 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Noonan, James P.
■5021 ▼aThesis (Ph.D.)--Yale University, 2025.
■520 ▼aHuman Accelerated Regions (HARs) are regulatory elements highly conserved across species but exhibit a significant excess of human-specific sequence changes. They include transcriptional enhancers with human-specific activity and have been implicated in the evolution of the human brain. However, our understanding of how HARs contributed to uniquely human features of the brain is hindered by a lack of insight into the genes and pathways that HARs regulate. It is unclear whether HARs acted by altering the expression of gene targets conserved between HARs and their chimpanzee orthologs or by gaining new gene targets in human, a mechanism termed enhancer hijacking. We generated a high-resolution map of chromatin interactions for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs) to comprehensively identify gene targets in both species. HARs and their chimpanzee orthologs targeted a conserved set of genes enriched for neurodevelopmental processes including neurogenesis and synaptic transmission. Changes in HAR enhancer activity were correlated with changes in conserved gene target expression. Conserved targets were enriched among genes differentially expressed between human and chimpanzee NSCs or between human and non-human primate brain. Species-specific HAR gene targets did not converge on known biological functions and were not significantly enriched among differentially expressed genes, suggesting that HARs did not alter gene expression via enhancer hijacking. HAR gene targets also showed cell type-specific expression patterns in the developing human brain, including outer radial glia, which are hypothesized to contribute to human cortical expansion. Our findings support that HARs influenced human brain evolution by altering the expression of conserved gene targets and provide the means to functionally link HARs with novel human brain features.
■590 ▼aSchool code: 0265.
■650 4▼aGenetics
■650 4▼aEvolution & development
■650 4▼aNeurosciences
■650 4▼aBiology
■653 ▼aHuman Accelerated Regions
■653 ▼aHuman brain evolution
■653 ▼aHuman Gain Enhancers
■653 ▼aNeurodevelopmental processes
■653 ▼aOuter radial glia
■690 ▼a0369
■690 ▼a0412
■690 ▼a0317
■690 ▼a0306
■71020▼aYale University▼bGenetics.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0265
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356759▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
