TIP60/P400/H4K12ac Plays a Role as a Heterochromatin Back-up Skeleton in Breast Cancer.

Abstract:

BACKGROUND/AIM:In breast cancer, initiation of carcinogenesis leads to epigenetic dysregulation, which can lead for example to the loss of the heterochromatin skeleton SUV39H1/H3K9me3/HP1 or the supposed secondary skeleton TIP60/P400/H4K12ac/BRD (2/4), which allows the maintenance of chromatin integrity and plasticity. This study investigated the relationship between TIP60, P400 and H4K12ac and their implications in breast tumors. MATERIALS AND METHODS:Seventy-seven patients diagnosed with breast cancer were included in this study. Chromatin immunoprecipitation (ChIP) assay was used to identify chromatin modifications. Western blot and reverse transcription and quantitative real-time PCR were used to determine protein and gene expression, respectively. RESULTS:We verified the variation in H4K12ac enrichment and the co-localization of H4K12ac and TIP60 on the euchromatin and heterochromatin genes, respectively, by ChIP-qPCR and ChIP-reChIP, which showed an enrichment of H4K12ac on specific genes in tumors compared to the adjacent healthy tissue and a co-localization of H4K12ac with TIP60 in different breast tumor types. Furthermore, RNA and protein expression of TIP60 and P400 was investigated and overexpression of TIP60 and P400 mRNA was associated with tumor aggressiveness. CONCLUSION:There is a potential interaction between H4K12ac and TIP60 in heterochromatin or euchromatin in breast tumors.

authors

Idrissou M,Boisnier T,Sanchez A,Khoufaf FZH,Penault-Llorca F,Bignon YJ,Bernard-Gallon D

doi

10.21873/cgp.20223

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

687-694

issue

6

eissn

1109-6535

issn

1790-6245

pii

17/6/687

journal_volume

17

pub_type

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