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Deregulation of the Ras-Erk Signalin...

Nabet, Behnam.

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Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape./
作者:	Nabet, Behnam.
面頁冊數:	150 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-02(E), Section: B.
Contained By:	Dissertation Abstracts International77-02B(E).
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3724335
ISBN:	9781339078106

Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape.
Nabet, Behnam.

Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape. - 150 p.

Source: Dissertation Abstracts International, Volume: 77-02(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2015.

Unrestrained receptor tyrosine kinase (RTK) signaling and epigenetic deregulation are root causes of tumorigenesis. We establish linkage between these processes by demonstrating that aberrant RTK signaling unleashed by oncogenic HRasG12V or loss of negative feedback through Sprouty gene deletion remodels histone modifications associated with active typical and super-enhancers. Abolishing unrestrained Ras-Erk signaling reverses the aberrant transcriptional program and diminishes histone 3 lysine 27 acetylation (H3K27ac) levels at deregulated enhancers. However, while both oncogenic HRasG12V and Sprouty deletion disrupt the Ras-Erk axis, the expression programs, enhancer signatures, and transcription factor networks modulated upon HRasG12V-transformation or Sprouty deletion are largely distinct. Oncogenic HRasG12V elevates H3K27ac levels at enhancers near the transcription factor Gata4 and the kinase Prkcb, as well as their expression levels. We show that Gata4 is necessary for the aberrant gene expression and H3K27ac marking at enhancers, and Prkcb is required for the oncogenic effects of HRas G12V-driven cells. BET bromodomain proteins and p300/CBP, which are chromatin regulators that recognize and deposit H3K27ac respectively, are also required for the oncogenic effects of HRasG12V-transformation. Taken together, our findings demonstrate that dynamic reprogramming of the cellular enhancer landscape is a major effect of oncogenic RTK signaling.

ISBN: 9781339078106Subjects--Topical Terms:

517296
Molecular biology.

Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape.
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