國立虎尾科技大學 |

Chromatin Regulators of MYC Oncoprotein Activity in Cancer.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Chromatin Regulators of MYC Oncoprotein Activity in Cancer./
Author:	Tu, William Bo Chen.
Description:	1 online resource (233 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 79-07(E), Section: B.
Contained By:	Dissertation Abstracts International79-07B(E).
Subject:	Molecular biology. -
Online resource:	click for full text (PQDT)
ISBN:	9780355537215

Chromatin Regulators of MYC Oncoprotein Activity in Cancer.
Tu, William Bo Chen.

Chromatin Regulators of MYC Oncoprotein Activity in Cancer. - 1 online resource (233 pages)

Source: Dissertation Abstracts International, Volume: 79-07(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2017.

Includes bibliographical references

The MYC oncoprotein is a key contributor to the development of virtually all cancer types. MYC is known as a global regulator of transcription that controls diverse physiological and oncogenic functions. Though there are 35 years' worth of research on this protein, mechanistic understanding and therapeutic targeting of MYC are still needed. We hypothesize that chromatin interactors are critical for MYC to achieve transcriptional control and biological outcomes. Our proteomic study of the MYC interactome yielded chromatin complexes and epigenetic regulators. In this thesis, we investigated two MYC-interacting complexes and defined the chromatin landscape of the MYC interactome. We characterized the novel interaction of MYC and the G9a histone methyltransferase and demonstrated their coordinated regulation of genome-wide transcriptional repression. This interaction and their resulting gene expression output support breast cancer growth, which is impaired with G9a inhibition. This study underscores the crucial role of epigenetics and epigenetic regulators in modulating MYC activity; this serves as the basis for a compelling strategy to target oncogenic MYC. We also interrogated the interaction of MYC and the SWI/SNF chromatin remodeling complex, whose many components are inactivated in a multitude of cancer types. We specifically showed the direct interaction of MYC and the INI1 subunit and their antagonistic relationship in regulating transcription and biological functions. Combining our proteomic approach with genome-wide resources, we established the chromatin landscape of the MYC interactome, defining chromatin profiles and target gene networks of known and novel MYC interactors. Collectively, these studies brought new insights to the understanding of MYC through the identification of novel chromatin interactors of MYC, their coordinated roles in regulating transcriptional activation and repression, their contributions to MYC-driven oncogenesis, and their therapeutic potential.

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

Mode of access: World Wide Web

ISBN: 9780355537215Subjects--Topical Terms:

583443
Molecular biology.
Index Terms--Genre/Form:

554714
Electronic books.

Chromatin Regulators of MYC Oncoprotein Activity in Cancer.
LDR:03254ntm a2200349Ki 4500 001 918634
005 20181030085011.5
006 m o u
007 cr mn||||a|a||
008 190606s2017 xx obm 000 0 eng d
020 $a 9780355537215
035 $a (MiAaPQ)AAI10289752
035 $a (MiAaPQ)toronto:15769
035 $a AAI10289752
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Tu, William Bo Chen. $3 1193006
245 1 0 $a Chromatin Regulators of MYC Oncoprotein Activity in Cancer.
264 0 $c 2017
300 $a 1 online resource (233 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertation Abstracts International, Volume: 79-07(E), Section: B.
500 $a Adviser: Linda Z. Penn.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2017.
504 $a Includes bibliographical references
520 $a The MYC oncoprotein is a key contributor to the development of virtually all cancer types. MYC is known as a global regulator of transcription that controls diverse physiological and oncogenic functions. Though there are 35 years' worth of research on this protein, mechanistic understanding and therapeutic targeting of MYC are still needed. We hypothesize that chromatin interactors are critical for MYC to achieve transcriptional control and biological outcomes. Our proteomic study of the MYC interactome yielded chromatin complexes and epigenetic regulators. In this thesis, we investigated two MYC-interacting complexes and defined the chromatin landscape of the MYC interactome. We characterized the novel interaction of MYC and the G9a histone methyltransferase and demonstrated their coordinated regulation of genome-wide transcriptional repression. This interaction and their resulting gene expression output support breast cancer growth, which is impaired with G9a inhibition. This study underscores the crucial role of epigenetics and epigenetic regulators in modulating MYC activity; this serves as the basis for a compelling strategy to target oncogenic MYC. We also interrogated the interaction of MYC and the SWI/SNF chromatin remodeling complex, whose many components are inactivated in a multitude of cancer types. We specifically showed the direct interaction of MYC and the INI1 subunit and their antagonistic relationship in regulating transcription and biological functions. Combining our proteomic approach with genome-wide resources, we established the chromatin landscape of the MYC interactome, defining chromatin profiles and target gene networks of known and novel MYC interactors. Collectively, these studies brought new insights to the understanding of MYC through the identification of novel chromatin interactors of MYC, their coordinated roles in regulating transcriptional activation and repression, their contributions to MYC-driven oncogenesis, and their therapeutic potential.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Molecular biology. $3 583443
650 4 $a Oncology. $3 593951
650 4 $a Cellular biology. $3 1148666
655 7 $a Electronic books. $2 local $3 554714
690 $a 0307
690 $a 0992
690 $a 0379
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of Toronto (Canada). $b Medical Biophysics. $3 1184111
773 0 $t Dissertation Abstracts International $g 79-07B(E).
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10289752 $z click for full text (PQDT)