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You searched for +publisher:"University of North Carolina" +contributor:("Mangum, Kevin"). One record found.

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University of North Carolina

1. Mangum, Kevin. Genetic and Epigenetic Mechanisms Regulating Smooth Muscle Cell Differentiation.

Degree: Pathology and Laboratory Medicine, 2017, University of North Carolina

Smooth muscle differentiation is a complex process, involving numerous molecular, genetic, and epigenetic mechanisms. Notably, smooth muscle cells (SMCs) retain marked plasticity in their ability to convert between synthetic and more differentiated contractile gene programs. In vascular diseases, including hypertension, atherosclerosis, and restenosis, SMCs dedifferentiate from their healthy, mature state to a more immature “phenotypically modulated” cell type capable of migrating, proliferating, and producing extracellular matrix, all of which contribute to disease. Additionally, genetic alterations in various components of the smooth muscle transcriptional machinery result in cardiovascular disease and even death. Thus, a more complete understanding of the exact mechanisms regulating SMC differentiation is crucial for the development of novel targets in the diagnosis and treatment of vascular disease. The work herein interrogates several points along the RhoA axis and defines their roles in SMC differentiation. First, the genetic and epigenetic mechanisms regulating expression of a smooth muscle-specific gene, GRAF3, are uncovered. GRAF3, also referred to as ARHGAP42, was first described by my collaborators in Joan Taylor’s Lab as a smooth muscle selective Rho-GAP essential for blood pressure control in mice. Single nucleotide polymorphisms in the GRAF3 gene were associated with changes in blood pressure, and the rs604723 T-allele variant located in a highly conserved DHS increased GRAF3 expression by promoting SRF binding to this region. In addition to SRF, we show that the transcription activity of this region as well as GRAF3 expression are controlled by the transcription factors, RBPJ and TEAD1. In subsequent chapters, we describe novel mechanisms regulating function of MRTF-A. Given that MRTF-A is essential for full activation of smooth muscle-specific gene expression, we hypothesize that these newly identified mechanisms regulate SMC differentiation. We describe our approach for identifying post-translational modifications and binding partners that regulate MRTF-A function. In our search for novel MRTF-A binding partners, we identified the putative histone lysine methyltransferase, PRDM6, and demonstrated that it was required for SMC differentiation. In overexpression experiments in COS-7 cells, we detected significant methylation on MRTF-A. Surprisingly, SMYD2 and SET7/9 strongly methylated MRTF-A, but PRDM6 did not. We found that SMDY2 methylated K27 within MRTF-A’s highly conserved basic nuclear localization signal. SMYD2-mediated methylation at K27 inhibited MRTF localization as well as MRTF-dependent activation of SMC transcription. Advisors/Committee Members: Mangum, Kevin, Mack, Christopher P., Bautch, Victoria, Liu, Jiandong, Sethupathy, Praveen, Taylor, Joan.

Subjects/Keywords: School of Medicine; Department of Pathology and Laboratory Medicine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Mangum, K. (2017). Genetic and Epigenetic Mechanisms Regulating Smooth Muscle Cell Differentiation. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:3e390865-999e-44be-b0f8-91bcda14f410

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Mangum, Kevin. “Genetic and Epigenetic Mechanisms Regulating Smooth Muscle Cell Differentiation.” 2017. Thesis, University of North Carolina. Accessed January 16, 2021. https://cdr.lib.unc.edu/record/uuid:3e390865-999e-44be-b0f8-91bcda14f410.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Mangum, Kevin. “Genetic and Epigenetic Mechanisms Regulating Smooth Muscle Cell Differentiation.” 2017. Web. 16 Jan 2021.

Vancouver:

Mangum K. Genetic and Epigenetic Mechanisms Regulating Smooth Muscle Cell Differentiation. [Internet] [Thesis]. University of North Carolina; 2017. [cited 2021 Jan 16]. Available from: https://cdr.lib.unc.edu/record/uuid:3e390865-999e-44be-b0f8-91bcda14f410.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mangum K. Genetic and Epigenetic Mechanisms Regulating Smooth Muscle Cell Differentiation. [Thesis]. University of North Carolina; 2017. Available from: https://cdr.lib.unc.edu/record/uuid:3e390865-999e-44be-b0f8-91bcda14f410

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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