Mass spectrometric studies on epigenetic interaction networks in cell differentiation

Lei Xiong, Agus Darwanto, Seema Sharma, Jason Herring, Shaoyan Hu, Maria Filippova, Valery Filippov, Yinsheng Wang, Chien Shing Chen, Penelope J. Duerksen-Hughes, Lawrence C. Sowers, Kangling Zhang

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Arrest of cell differentiation is one of the leading causes of leukemia and other cancers. Induction of cell differentiation using pharmaceutical agents has been clinically attempted for the treatment of these cancers. Epigenetic regulation may be one of the underlying molecular mechanisms controlling cell proliferation or differentiation. Here, we report on the use of proteomics-based differential protein expression analysis in conjunction with quantification of histone modifications to decipher the interconnections among epigenetic modifications, their modifying enzymes or mediators, and changes in the associated pathways/networks that occur during cell differentiation. During phorbol-12-myristate 13-acetate-induced differentiation of U937 cells, fatty acid synthesis and its metabolic processing, the clathrin-coated pit endocytosis pathway, and the ubiquitin/26 S proteasome degradation pathways were up-regulated. In addition, global histone H3/H4 acetylation and H2B ubiquitination were down-regulated concomitantly with impaired chromatin remodeling machinery, RNA polymerase II complexes, and DNA replication. Differential protein expression analysis established the networks linking histone hypoacetylation to the down-regulated expression/activity of p300 and linking histone H2B ubiquitination to the RNA polymerase II-associated FACT-RTF1- PAF1 complex. Collectively, our approach has provided an unprecedentedly systemic set of insights into the role of epigenetic regulation in leukemia cell differentiation.

Original languageEnglish (US)
Pages (from-to)13657-13668
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number15
DOIs
StatePublished - Apr 15 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Xiong, L., Darwanto, A., Sharma, S., Herring, J., Hu, S., Filippova, M., Filippov, V., Wang, Y., Chen, C. S., Duerksen-Hughes, P. J., Sowers, L. C., & Zhang, K. (2011). Mass spectrometric studies on epigenetic interaction networks in cell differentiation. Journal of Biological Chemistry, 286(15), 13657-13668. https://doi.org/10.1074/jbc.M110.204800