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DNA sequence and epigenetic features...

Boston University.

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DNA sequence and epigenetic features that drive human promoter function.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	DNA sequence and epigenetic features that drive human promoter function./
作者:	Landolin, Jane Marie.
面頁冊數:	93 p.
附註:	Adviser: Zhiping Weng.
Contained By:	Dissertation Abstracts International69-07B.
標題:	Biology, Bioinformatics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3323127
ISBN:	9780549750888

DNA sequence and epigenetic features that drive human promoter function.
Landolin, Jane Marie.

DNA sequence and epigenetic features that drive human promoter function. - 93 p.

Adviser: Zhiping Weng.

Thesis (Ph.D.)--Boston University, 2009.

The human genome contains approximately three billion bases that instruct cells to produce proteins. Varying levels of proteins inside of cells affect the function of tissues and organs, and eventually influence the health and behavior of individuals. One of the first steps in this chain of events happens at the molecular level, when DNA is transcribed into RNA. Promoters contain the necessary and sufficient information for cells to initiate transcription. Interspersed along promoters are 6 to 10 base sequence motifs that are bound by transcription factors (TFs), which activate or repress transcription of downstream genes. Epigenetic marks such as CpG methylation and modified histones can also affect transcription by interacting with TFs. As the sequence of the Human genome is now known, and experimental techniques to map epigenetic marks genome-wide are now being attempted, we have an unprecedented opportunity to study of transcription regulation with both breadth and depth.

ISBN: 9780549750888Subjects--Topical Terms:

1018415
Biology, Bioinformatics.

DNA sequence and epigenetic features that drive human promoter function.
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245 1 0 $a DNA sequence and epigenetic features that drive human promoter function.
300 $a 93 p.
500 $a Adviser: Zhiping Weng.
500 $a Source: Dissertation Abstracts International, Volume: 69-07, Section: B, page: 4291.
502 $a Thesis (Ph.D.)--Boston University, 2009.
520 $a The human genome contains approximately three billion bases that instruct cells to produce proteins. Varying levels of proteins inside of cells affect the function of tissues and organs, and eventually influence the health and behavior of individuals. One of the first steps in this chain of events happens at the molecular level, when DNA is transcribed into RNA. Promoters contain the necessary and sufficient information for cells to initiate transcription. Interspersed along promoters are 6 to 10 base sequence motifs that are bound by transcription factors (TFs), which activate or repress transcription of downstream genes. Epigenetic marks such as CpG methylation and modified histones can also affect transcription by interacting with TFs. As the sequence of the Human genome is now known, and experimental techniques to map epigenetic marks genome-wide are now being attempted, we have an unprecedented opportunity to study of transcription regulation with both breadth and depth.
520 $a In this dissertation, I present several studies examining regulatory signals from DNA sequence as well as epigenetic marks. The first study identifies TFs and modified histones that are important for regulating bidirectional promoters in the human genome. The second study models tissue-specific transcription regulation using TF sequence motifs and CpG methylation. Building upon the biological principles discovered in the first two studies, the third study computationally predicts TF binding footprints, which are then tested experimentally by mutagenesis.
520 $a GA-binding protein (GABP) is an important TF identified in all three studies. The analysis presented in this dissertation shows that GABP is a major regulator of bidirectional promoters, and activates genes that are ubiquitously transcribed. The motif for GABP is a good predictor of in vivo binding, and mutagenesis confirms that our TF footprint predictions are indeed functional, with average 3-fold knock down of promoter activity compared to wild-type.
520 $a The analysis was possible because DNA sequence signals were decoupled from epigenetic marks using a transient transfection promoter activity assay system. This work demonstrates the importance of computation in analyzing biological data from different types of high-throughput experiments, and provides the foundation for a single-base-resolution map of TF binding footprints in the Human genome.
590 $a School code: 0017.
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791 $a Ph.D.
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