Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Histone Modifiers

Abstract A17: Glycosaminoglycans regulates histone acetylation status in multiple myeloma

Anurag Purushothaman and Ralph D. Sanderson
Anurag Purushothaman
University of Alabama at Birmingham, Birmingham, AL.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ralph D. Sanderson
University of Alabama at Birmingham, Birmingham, AL.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1538-7445.CEC13-A17 Published July 2013
  • Article
  • Info & Metrics
Loading

Abstract

Histone acetylation modulates gene expression, cellular differentiation, and cell survival and is regulated by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC inhibition results in accumulation of acetylated nucleosomal histones and induces differentiation and/or apoptosis in transformed cells and therefore HADC inhibitors are being actively studied as novel therapies in multiple myeloma. However, the mechanisms that regulate the acetylation levels of histones in myeloma remain unclear. We recently discovered that glycosaminoglycan (GAGs) chains of myeloma cells play an important role in regulating histone acetylation status. GAGs, such as chondroitin sulfate and heparan sulfate, which are expressed in the form serglycin and syndecan-1 proteoglycans, respectively, are highly expressed by myeloma cells and are present in the nucleus of these cells. Because exogenous GAGs are shown to both inhibit HAT activity and bind to the acetylation sites of histones, we hypothesized that reduction in GAGs would increase HAT activity and histone acetylation. We found that removal of GAGs from the nucleus of myeloma cells either by treatment with GAG degrading bacterial enzymes or by expressing the heparan sulfate degrading enzyme heparanase, significantly increased HAT activity and histone acetylation in myeloma cells. Further, the levels of acetylated histones are highly upregulated in tumors formed from cells expressing high levels of heparanase or cells that are silenced for syndecan-1 expression. BIACore assay showed that both chondroitin and heparan sulfates strongly bind to HAT enzyme p300. By dot blot assay we also demonstrate that both syndecan-1 and serglycin bind strongly to histones. Previous studies have shown that the negatively charged GAGs can bind to positively charged lysine residues (acetylation sites) on histone proteins. Overall our findings clearly demonstrate that GAGs decreases histone acetylation by both inhibiting HAT activity and by binding to acetylation sites of histones. This represents a novel mechanism for histone hypoacetylation, which is traditionally considered due to HDAC activity.

Citation Format: Anurag Purushothaman, Ralph D. Sanderson. Glycosaminoglycans regulates histone acetylation status in multiple myeloma. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A17.

  • ©2013 American Association for Cancer Research.
Back to top
Cancer Research: 73 (13 Supplement)
July 2013
Volume 73, Issue 13 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract A17: Glycosaminoglycans regulates histone acetylation status in multiple myeloma
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract A17: Glycosaminoglycans regulates histone acetylation status in multiple myeloma
Anurag Purushothaman and Ralph D. Sanderson
Cancer Res July 1 2013 (73) (13 Supplement) A17; DOI: 10.1158/1538-7445.CEC13-A17

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract A17: Glycosaminoglycans regulates histone acetylation status in multiple myeloma
Anurag Purushothaman and Ralph D. Sanderson
Cancer Res July 1 2013 (73) (13 Supplement) A17; DOI: 10.1158/1538-7445.CEC13-A17
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Histone Modifiers

  • Abstract IA08: Targeting histone methylation in leukemia
  • Abstract IA02: Varying and poisoning the “Histone Code”: A role of the histone variant H3.3 in human cancers
  • Abstract IA06: Epigenetic regulation and heterogeneity in cancer
Show more 3

Histone Modifiers: Poster Presentations - Proffered Abstracts

  • Abstract A18: The role of histone demethylase JARID1C in tumorigenesis of clear cell renal cell carcinoma
  • Abstract A20: IDH mutations and 2-HG selectively affect histone methylation in the endogenous setting
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement