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postgraduate thesis: Screening and characterization of putative gene enhancers during craniofacial development
Title | Screening and characterization of putative gene enhancers during craniofacial development |
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Authors | |
Advisors | |
Issue Date | 2017 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Wu, Z. [伍昭明]. (2017). Screening and characterization of putative gene enhancers during craniofacial development. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Craniofacial anormalies are among the most common congenital diseases. Craniofacial development is a complex procedure which requires fine regulation of the expression of many genes. Although the functions of many of these genes have been extensively studied, the mechanisms underlying their control of expression are not well understood. Enhancers are non-coding regulatory sequences that can enhance the expression of their target genes. They are believed to play a crucial role
in the regulation of gene expression during the developmental process, and also in the evolution of different traits. Despite their potential important roles, not many craniofacial enhancers have been identified and characterized.
To identify enhancers that are involved in craniofacial development and evolution, a comparative, genome-wide screening of the enhancer signature H3K27ac in the frontonasal process (FNP) of chicken and duck embryos was carried out. A few
putative enhancers of H3K27ac enrichment were validated and characterized in chicken.
In Chapter 2, Chromatin Immunoprecipitation-sequencing (ChIP-seq) targeting H3K27ac in the FNP of Hamburger Hamilton (HH) stage 26-27 chicken and duck were conducted to search for putative enhancers. Through processing and analysis of the sequencing data, 13,816 and 6,059 H3K27ac enriched regions were identified in the genomes of chicken and duck respectively. Many of the H3K27ac enriched regions were flanked by important craniofacial development genes. Cross-referencing the chicken and duck datasets suggested that more than 60% of the H3K27ac enriched regions were overlapped between chicken and duck in the FNP at HH stage 26-27.
In Chapter 3, 10 putative enhancers were selected from the H3K27ac enriched regions that were identified in Chapter 2. The putative enhancers were cloned into an enhancer reporter, and their activaties during craniofacial development were
examined. consistent enhancer activities were observed in 4 of the enhancers. The target genes of these enhancers were determined by their topologically associating domains (TAD) and the expression patterns of their putative target genes. The targets of these enhancers include craniofacial development related genes BMP4, LEF1, SIX1 and SIX4, suggesting their potential importance in craniofacial development and evolution.
The screening and characterization of these enhancers provided us clues about the regulations and variations of craniofacial gene expression during development, leading to a more fundamental understanding of craniofacial development and evolution. |
Degree | Doctor of Philosophy |
Subject | Skull - Abnormalities - Genetic aspects |
Dept/Program | Dentistry |
Persistent Identifier | http://hdl.handle.net/10722/255086 |
DC Field | Value | Language |
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dc.contributor.advisor | Jung, HS | - |
dc.contributor.advisor | Tanaka, R | - |
dc.contributor.author | Wu, Zhaoming | - |
dc.contributor.author | 伍昭明 | - |
dc.date.accessioned | 2018-06-21T03:42:11Z | - |
dc.date.available | 2018-06-21T03:42:11Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Wu, Z. [伍昭明]. (2017). Screening and characterization of putative gene enhancers during craniofacial development. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/255086 | - |
dc.description.abstract | Craniofacial anormalies are among the most common congenital diseases. Craniofacial development is a complex procedure which requires fine regulation of the expression of many genes. Although the functions of many of these genes have been extensively studied, the mechanisms underlying their control of expression are not well understood. Enhancers are non-coding regulatory sequences that can enhance the expression of their target genes. They are believed to play a crucial role in the regulation of gene expression during the developmental process, and also in the evolution of different traits. Despite their potential important roles, not many craniofacial enhancers have been identified and characterized. To identify enhancers that are involved in craniofacial development and evolution, a comparative, genome-wide screening of the enhancer signature H3K27ac in the frontonasal process (FNP) of chicken and duck embryos was carried out. A few putative enhancers of H3K27ac enrichment were validated and characterized in chicken. In Chapter 2, Chromatin Immunoprecipitation-sequencing (ChIP-seq) targeting H3K27ac in the FNP of Hamburger Hamilton (HH) stage 26-27 chicken and duck were conducted to search for putative enhancers. Through processing and analysis of the sequencing data, 13,816 and 6,059 H3K27ac enriched regions were identified in the genomes of chicken and duck respectively. Many of the H3K27ac enriched regions were flanked by important craniofacial development genes. Cross-referencing the chicken and duck datasets suggested that more than 60% of the H3K27ac enriched regions were overlapped between chicken and duck in the FNP at HH stage 26-27. In Chapter 3, 10 putative enhancers were selected from the H3K27ac enriched regions that were identified in Chapter 2. The putative enhancers were cloned into an enhancer reporter, and their activaties during craniofacial development were examined. consistent enhancer activities were observed in 4 of the enhancers. The target genes of these enhancers were determined by their topologically associating domains (TAD) and the expression patterns of their putative target genes. The targets of these enhancers include craniofacial development related genes BMP4, LEF1, SIX1 and SIX4, suggesting their potential importance in craniofacial development and evolution. The screening and characterization of these enhancers provided us clues about the regulations and variations of craniofacial gene expression during development, leading to a more fundamental understanding of craniofacial development and evolution. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Skull - Abnormalities - Genetic aspects | - |
dc.title | Screening and characterization of putative gene enhancers during craniofacial development | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Doctor of Philosophy | - |
dc.description.thesislevel | Doctoral | - |
dc.description.thesisdiscipline | Dentistry | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_991044014364503414 | - |
dc.date.hkucongregation | 2018 | - |
dc.identifier.mmsid | 991044014364503414 | - |