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Establishment and Regulation of Epithelial Enhancers by P63
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Establishment and Regulation of Epithelial Enhancers by P63. |
| 개인저자 | Lin Shiao, Enrique. |
| 단체저자명 | University of Pennsylvania. Biochemistry and Molecular Biophysics. |
| 발행사항 | [S.l.]: University of Pennsylvania., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 133 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781088391747 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Includes supplementary digital materials. Advisor: Berger, Shelley L. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | The transcription factor p63 is a key mediator of epidermal commitment, development, and differentiation. Point mutations in p63 in human patients lead to developmental defects, including orofacial clefting, one of the most common congenital defects in humans. To date, knowledge is limited about how pivotal is p63's role in human craniofacial development, due in part to a lack of tractable models to study de novo expression of p63 and its role at developmentally regulated genes. Using an inducible trans-differentiation model, combined with epigenomic sequencing and multi-cohort meta-analysis of GWAS data, we show that p63 establishes enhancers at craniofacial development genes to modulate their transcription. We further identify histone methyltransferase KMT2D as a key interacting partner of p63 at these enhancers and identify a novel role for this histone methyltransferase in maintaining epithelial homeostasis. Our results demonstrate that disease-specific substitution mutation in the DNA binding domain or SAM protein interaction domain of p63 respectively eliminate or reduce establishment of these enhancers. Finally, we show enhancers established by p63 are highly enriched for SNPs associated with nonsyndromic cleft lip +/- cleft palate (CL/P). These orthogonal approaches indicate a strong molecular link between p63 enhancer function and CL/P, illuminating molecular mechanisms underlying this developmental defect and revealing vital regulatory elements and new candidate causative genes. |
| 일반주제명 | Genetics. Developmental biology. Biochemistry. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
