TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer

Epigenomics. 2018 Nov;10(11):1415-1430. doi: 10.2217/epi-2018-0004. Epub 2018 Oct 16.


Aim: The acetyltransferase TIP60 is reported to be downregulated in several cancers, in particular breast cancer, but the molecular mechanisms resulting from its alteration are still unclear.

Materials & methods: In breast tumors, H3K4ac enrichment and its link with TIP60 were evaluated by chromatin immunoprecipitation-qPCR and re-chromatin immunoprecipitation techniques. To assess the biological roles of TIP60 in breast cancer, two cell lines of breast cancer, MDA-MB-231 (ER-) and MCF-7 (ER+) were transfected with shRNA specifically targeting TIP60 and injected to athymic Balb-c mice.

Results: We identified a potential target of TIP60, H3K4. We show that an underexpression of TIP60 could contribute to a reduction of H3K4 acetylation in breast cancer. An increase in tumor development was noted in sh-TIP60 MDA-MB-231 xenografts and a slowdown of tumor growth in sh-TIP60 MCF-7 xenografts.

Conclusion: This is evidence that the underexpression of TIP60 observed in breast cancer can promote the tumorigenesis of ER-negative tumors.

Keywords: H3K4ac; acetyltransferase TIP60; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Female
  • Histone Code*
  • Histones / metabolism*
  • Humans
  • Lysine Acetyltransferase 5 / genetics
  • Lysine Acetyltransferase 5 / metabolism*
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude


  • Histones
  • KAT5 protein, human
  • Lysine Acetyltransferase 5