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Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .


Idrissou, Mouhamed and Lebert, Andre and Boisnier, Tiphanie and Sanchez,Anna and Houfaf Khoufaf, Fatma Zohra and Penault-Llorca, Frédérique andBignon, Yves-Jean and Bernard-Gallon, Dominique

Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic protein acts in several cellular pathways by acetylating proteins. RNA and protein expressions of TIP60 were shown to decrease in some breast cancer subtypes, particularly in triple-negative breast cancer (TNBC), where a low expression of TIP60 was exhibited compared with luminal subtypes. In this study, the inhibition of the residual activity of TIP60 in breast cancer cell lines was investigated by using two chemical inhibitors, TH1834 and NU9056, first on the acetylation of the specific target, lysine 4 of histone 3 (H3K4) by immunoblotting, and second, by chromatin immunoprecipitation (ChIP)-qPCR (-quantitative Polymerase Chain Reaction). Subsequently, significant decreases or a trend toward decrease of H3K4ac in the different chromatin compartments were observed. In addition, the expression of 48 human nuclear receptors was studied with TaqMan Low-Density Array in these breast cancer cell lines treated with TIP60 inhibitors. The statistical analysis allowed us to comprehensively characterize the androgen receptor and receptors in TNBC cell lines after TH1834 or NU9056 treatment. The understanding of the residual activity of TIP60 in the evolution of breast cancer might be a major asset in the fight against this disease, and could allow TIP60 to be used as a biomarker or therapeutic target for breast cancer progression in the future.

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Antibody
IP-Star Compact
iDeal ChIP-seq Kit for Histones

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Published
October, 2020

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Products used in this publication

  • cut and tag antibody icon
    C15410003-50
    H3K4me3 polyclonal antibody
  • Mouse IgG
    C15410206
    Rabbit IgG
  • Compact Automated System
    B03000002
    SX-8G IP-Star® Compact Automated System
  • ChIP kit icon
    C01010171
    Auto iDeal ChIP-seq kit for Histones
  • default alt
    C03040001
    MicroChIP DiaPure columns
  • default alt
    C17011047-50
    Human ChIP-seq grade GAPDH TSS primer pair
  • default alt
    C17011006-50
    Human ChIP-seq grade Myoglobin Exon 2 primer pair

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