國立虎尾科技大學 |

Determining the mechanistics of chromatin regulated p63 targeting using next-generation sequencing methods.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	Determining the mechanistics of chromatin regulated p63 targeting using next-generation sequencing methods./
作者:	Sethi, Isha.
面頁冊數:	1 online resource (161 pages)
附註:	Source: Dissertation Abstracts International, Volume: 78-03(E), Section: B.
Contained By:	Dissertation Abstracts International78-03B(E).
標題:	Biochemistry. -
電子資源:	click for full text (PQDT)
ISBN:	9781369184693

Determining the mechanistics of chromatin regulated p63 targeting using next-generation sequencing methods.
Sethi, Isha.

Determining the mechanistics of chromatin regulated p63 targeting using next-generation sequencing methods. - 1 online resource (161 pages)

Source: Dissertation Abstracts International, Volume: 78-03(E), Section: B.

Thesis (Ph.D.)--State University of New York at Buffalo, 2016.

Includes bibliographical references

Transcriptional regulation is a process that through complex interplay between cis-regulatory regions, trans-acting factors, chromatin features and higher-order genome organization leads to the implementation of lineage-specific gene expression programs. It is very important to accurately understand this process because any aberrations can lead to severe diseases. I have primarily studied the mechanistics of transcriptional regulation with relation to p63, a TF critical for epidermal morphogenesis. P63 mutations and overexpression has been linked to many development disorders and epithelial cancers, making it imperative to decipher the rules that dictate how p63 chooses its target genes and regulates myriad signaling pathways. I have employed Next-Generation sequencing methods to gain a global understanding of the p63 regulatory landscape and the many cogs modulating p63's functions.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9781369184693Subjects--Topical Terms:

582831
Biochemistry.
Index Terms--Genre/Form:

554714
Electronic books.

Determining the mechanistics of chromatin regulated p63 targeting using next-generation sequencing methods.
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500 $a Source: Dissertation Abstracts International, Volume: 78-03(E), Section: B.
500 $a Advisers: Michael J. Buck; Satrajit Sinha.
502 $a Thesis (Ph.D.)--State University of New York at Buffalo, 2016.
504 $a Includes bibliographical references
520 $a Transcriptional regulation is a process that through complex interplay between cis-regulatory regions, trans-acting factors, chromatin features and higher-order genome organization leads to the implementation of lineage-specific gene expression programs. It is very important to accurately understand this process because any aberrations can lead to severe diseases. I have primarily studied the mechanistics of transcriptional regulation with relation to p63, a TF critical for epidermal morphogenesis. P63 mutations and overexpression has been linked to many development disorders and epithelial cancers, making it imperative to decipher the rules that dictate how p63 chooses its target genes and regulates myriad signaling pathways. I have employed Next-Generation sequencing methods to gain a global understanding of the p63 regulatory landscape and the many cogs modulating p63's functions.
520 $a Deciphering the exact role played by p63 has been complicated due to the presence of its many isoforms (TAp63 (alpha, beta, gamma), DeltaNp63 (alpha, beta, gamma). I therefore commenced my research with mapping the transcriptomic landscape of human cell-lines and tissues and thereby establishing that the DeltaNp63alpha isoform is the main workhorse regulating epidermal morphogenesis. I next employed the power of publicly available Next-Generation sequencing datasets in concert with in-silico analysis to analyze on a genome-wide level how this p63 variant chooses its target genes. I comprehensively analyzed human keratinocyte datasets for all key features dictating p63 targeting including the underlying DNA-sequence, p63-chromatin interactions and myriad possible co-ordinating TFs. Among other findings, this study provided preliminary evidence about p63 binding being a possible first event in making a regulatory region active and functional. I finally tested the consistency of the p63 regulatory landscape across evolution by mapping p63 targets and the chromatin microenvironment in mouse keratinocytes and comparing it to homologous regions in human keratinocytes. Strikingly, it seemed that the evolutionary forces wreak havoc with the p63 enhancer network, changing it drastically between mouse and human. This also leads to massive re-wiring of the epigenetic landscape. To ascertain whether changed p63 targeting also contributes to differential transcriptional output, I lastly mapped and compared the expression levels of human and mouse p63 target genes. This study was very important because it suggested that the p63 gene networks are different between species, providing a possible molecular explanation for observed phenotypic differences in epidermal morphogenesis between human and mouse.
520 $a The work presented in this thesis not only provides a comprehensive understanding of p63 TF regulation but can also act as a launching pad for many research questions. It can be built upon to investigate the cause vs. effect of p63 targeting. The effect of mutations or overexpression, as seen in diseases, can be studied for their effect on p63 binding. Finally, using isoform-specific antibodies, the rules governing the targeting of other variants like the TA isoforms can also be deciphered.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Biochemistry. $3 582831
650 4 $a Bioinformatics. $3 583857
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