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Combinatorial Regulation By Enzymes that Modulate the Chromatin Landscape and Gene Expression
Başlık:
Combinatorial Regulation By Enzymes that Modulate the Chromatin Landscape and Gene Expression
Yazar:
Runge, John Stevens, author.
ISBN:
9780438033634
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (192 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Terry Magnuson Committee members: Mauro Calabrese; Gregory E. Crawford; Ian J. Davis; William Y. Kim.
Özet:
The eukaryotic genome is stored in the nucleus as chromatin, a dynamic structure of DNA and histone proteins. Chromatin contains a vast array of features that directs how, when, and where genomic DNA is made accessible by regulatory machinery. These features facilitate homeostatic cell programs, whereas their misregulation is a hallmark of cancer where endogenous regulatory programs are co-opted to promote aberrant signaling.
In Chapter 1, I introduce four classes of proteins and protein complexes, among others, that regulate chromatin. I describe seminal discoveries that indicate these classes operate within elaborate networks that direct genomic output. In Chapter 2, I outline the roles that the class of ATP-dependent chromatin remodeling enzymes, nicknamed movers, serves in chromatin regulation. Chapters 3 and 4 describe our ongoing efforts to elucidate the mechanism by which a mover, named INO80-C, targets chromatin and identifies suitable genomic loci for regulation. We leveraged genomics approaches, biochemistry, and molecular biology to characterize the genomic targeting and molecular function of INO80-C in human cells. Chapter 3 details our observation that INO80-C is not a uniform biochemical complex at all sites across the genome, in contrast to expectations based on the literature. Chapter 4 demonstrates our efforts to delineate the function of INO80-C at its genomic targets, including our exploration of an antagonistic relationship with a histone methyltransferase named Polycomb Repressive Complex 2. Collectively, these data indicate that INO80-C engages in meaningful crosstalk with other chromatin regulators and features at its genomic targets. In Chapter 5, I draw conclusions from my research and place the findings into a broader context. Additionally, I describe the implications that my work may have on translational topics, with an emphasis on cancer biology.
Notlar:
School code: 0153
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(678508.1) | 678508-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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