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Proteomic Characterization of Linker Histone Variants in Breast Cancer

Hoover, Michael
http://rave.ohiolink.edu/etdc/view?acc_num=osu1497604765734645

Abstract Details

2017, Doctor of Philosophy, Ohio State University, Biomedical Sciences.
Central to our understanding of the heritability of our genetic information is the compaction of DNA within the nuclei of all our cells. Linker histones work in conjunction with the core histones to package DNA and impact the expression of genes associated with countless cellular processes. There are 11 sequence variants of linker histones present in humans, a consideration that complicates their analysis and has delayed our understanding of their biology. Like many other proteins, linker histones acquire chemical modifications that change their biophysical properties and confer biological direction to the cellular machinery. By extending our knowledge of how and when these sequence variants are modified, we can begin to understand in greater detail what roles the linker histones are playing in specific cellular contexts. Chapter 1 describes the context in which we are studying the linker histones and how these proteins are related to carcinogenesis. Further, we introduce proteomics as a tool for studying linker histone proteins and quantifying the degree to which they are modified. Chapter 2 highlights our use of mass spectrometry to characterize major linker histone variants and their modified forms in breast epithelial and cancer cells. Our results suggest that linker histones are modified non-stochastically, as we observe modifications that occur sequentially and with variant specificity. In Chapter 3, we discuss preliminary efforts to develop methodology to enrich individual linker histone variants. Our enduring goal is to understand how these modifications confer function and vary the ability of linker histones to bind other important proteins. Collectively, this work has advanced our knowledge of individual linker histone proteins and provided the framework to progressively advance our understanding of linker histone and chromatin biology.
Michael A. Freitas, PhD (Advisor)
David P. Carbone, MD, PhD (Committee Member)
Paul K. Herman, PhD (Committee Member)
Thomas Ludwig, PhD (Committee Member)
190 p.
Biomedical Research

Recommended Citations

Citations

  • Hoover, M. (2017). Proteomic Characterization of Linker Histone Variants in Breast Cancer [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1497604765734645

    APA Style (7th edition)

  • Hoover, Michael. Proteomic Characterization of Linker Histone Variants in Breast Cancer. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1497604765734645.

    MLA Style (8th edition)

  • Hoover, Michael. "Proteomic Characterization of Linker Histone Variants in Breast Cancer." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1497604765734645

    Chicago Manual of Style (17th edition)

osu1497604765734645
178
© 2017, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.