Selenite and methylseleninic acid epigenetically affects distinct gene sets in myeloid leukemia: A genome wide epigenetic analysis.

Khalkar P, Ali HA, Codó P, Argelich ND, Martikainen A, Arzenani MK, Lehmann S, Walfridsson J, Ungerstedt J, Fernandes AP

Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq). Both selenite and MSA had major effects on histone marks but the effects of MSA were more pronounced. Gene ontology analysis revealed that selenite affected genes involved in response to oxygen and hypoxia, whereas MSA affected distinct gene sets associated with cell adhesion and glucocorticoid receptors, also apparent by global gene expression analysis using RNA sequencing. The correlation to adhesion was functionally confirmed by a significantly weakened ability of MSA treated cells to attach to fibronectin and linked to decreased expression of integrin beta 1. A striking loss of cellular adhesion was also confirmed in primary patient AML cells. Recent strategies to enhance the cytotoxicity of chemotherapeutic drugs by disrupting the interaction between leukemic and stromal cells in the bone marrow are of increasing interest; and organic selenium compounds like MSA might be promising candidates. In conclusion, these results provide new insight on the mechanism of action of selenium compounds, and will be of value for the understanding, usage, and development of new selenium compounds as anticancer agents.

iDeal ChIP-seq Kit for Histones

Share this article

March, 2018


Products used in this publication

  • ChIP kit icon
    iDeal ChIP-seq kit for Histones
  • some alt
    1.5 ml Bioruptor® Plus TPX microtubes
  • some alt
    1.5 ml Bioruptor® Plus TPX microtubes


  • London Calling 2024
    London, UK
    May 21-May 24, 2024
  • Symposium of the Young Scientist Association
    Vienna, Austria
    May 28-May 29, 2024
  • ESHG 2024
    Berlin, Germany
    Jun 1-Jun 4, 2024
  • CLEPIC 2024
    Warsaw, Poland
    Jun 5-Jun 7, 2024
  • EACR 2024
    Rotterdam, Netherlands
    Jun 10-Jun 13, 2024
  • Chromatin meets South 2024
    Marseille, France
    Jun 13-Jun 14, 2024
 See all events


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics