NDLI: Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma.

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Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sengupta, Deepanwita Byrum, Stephanie D. Avaritt, Nathan L. Davis, Lauren Shields, Bradley Mahmoud, Fade Reynolds, Matthew Orr, Lisa M. Mackintosh, Samuel G. Shalin, Sara C. Tackett, Alan J.
Description	Author Affiliation: Sengupta D ( From the Department of Biochemistry and Molecular Biology.); Byrum SD ( From the Department of Biochemistry and Molecular Biology.); Avaritt NL ( From the Department of Biochemistry and Molecular Biology.); Davis L ( From the Department of Biochemistry and Molecular Biology.); Shields B ( From the Department of Biochemistry and Molecular Biology.); Mahmoud F ( ¶Department of Hematology Oncology and Internal Medicine, and.); Reynolds M ( From the Department of Biochemistry and Molecular Biology.); Orr LM ( From the Department of Biochemistry and Molecular Biology.); Mackintosh SG ( From the Department of Biochemistry and Molecular Biology.); Shalin SC ( âDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 ajtackett@uams.edu scshalin@uams.edu.); Tackett AJ ( From the Department of Biochemistry and Molecular Biology, âDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 ajtackett@uams.edu scshalin@uams.edu.)
Abstract	Normal cell growth is characterized by a regulated epigenetic program that drives cellular activities such as gene transcription, DNA replication, and DNA damage repair. Perturbation of this epigenetic program can lead to events such as mis-regulation of gene transcription and diseases such as cancer. To begin to understand the epigenetic program correlated to the development of melanoma, we performed a novel quantitative mass spectrometric analysis of histone post-translational modifications mis-regulated in melanoma cell culture as well as patient tumors. Aggressive melanoma cell lines as well as metastatic melanoma were found to have elevated histone H3 Lys(27) trimethylation (H3K27me3) accompanied by overexpressed methyltransferase EZH2 that adds the specific modification. The altered epigenetic program that led to elevated H3K27me3 in melanoma cell culture was found to directly silence transcription of the tumor suppressor genes RUNX3 and E-cadherin. The EZH2-mediated silencing of RUNX3 and E-cadherin transcription was also validated in advanced stage human melanoma tissues. This is the first study focusing on the detailed epigenetic mechanisms leading to EZH2-mediated silencing of RUNX3 and E-cadherin tumor suppressors in melanoma. This study underscores the utility of using high resolution mass spectrometry to identify mis-regulated epigenetic programs in diseases such as cancer, which could ultimately lead to the identification of biological markers for diagnostic and prognostic applications.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
Journal	Molecular & Cellular Proteomics
Issue Number	3
Volume Number	15
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2016-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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