SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human breast cancer

Rifaï, Khaldoun; Judes, Gaëlle; Idrissou, Mouhamed; Daures, Marine; Bignon, Yves‐Jean; Penault‐Llorca, Frédérique; Bernard‐Gallon, Dominique

doi:10.18632/oncotarget.25771

Cited by 47 publications

(33 citation statements)

References 53 publications

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“…Chromatin immunoprecipitation (ChIP) assays and Quantitative real-time PCR method and data analysis. ChIP assays were performed on chromatin extracted from breast tumors using the Auto iDeal ChIP-seq kit for Histones (C01010171, Diagenode, Seraing, Belgium) according to manufacturer's instructions and the experimental setup developed in our laboratory (20,21). The antibodies used were 3 μg of anti-H4k12ac Abs (C15200218, Diagenode) and 1 μg non-immune rabbit IgG (Kch-504-250, Diagenode) serving as a negative control.…”

Section: Methodsmentioning

confidence: 99%

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

Idrissou

Boisnier

Sánchez

et al. 2020

Cancer Genomics Proteomics

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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 colocalization 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. Breast cancer is the most frequent cancer (24.2% new cases in 2018) and the leading cause of cancer-related death (15% in 2018) (1). The majority of breast cancers are sporadic (non-hereditary), representing 80 to 90% of breast cancers (2). Deregulation of chromatin integrity and plasticity is among the causes of sporadic cancer (3). They occur at the epigenetic level in the different compartments of chromatin, which are heterochromatin (compacted chromatin) that inhibits gene expression, and euchromatin (relaxed chromatin) that promotes gene transcription. These chromatin states are maintained by so-called epigenetic proteins, which, by placing groups or marks on the histones, allow entry or exit from one state to another (4-6). Among these proteins, SUV39H1, which is a histone methyltransferase (HMT) that adds the H3K9me3 marker on the site where the HP1 protein will bind, thus forming the SUV39H1/H3K9me3/HP1 skeleton which keeps the chromatin closed and inhibits transcription in the heterochromatin region (7, 8). Heterochromatin houses inactive genes such as numerous oncogenes; the loss of this structure would lead to the transcription of oncogenes. Several studies have shown a loss of the SUV39H1 protein in cancer, but also a loss of the SUV39H1/H3K9me3/HP1 skeleton during the onset of carcinogenesis (7, 9). The acetyl-transferases (HAT) such as TIP60 are able to add acetyl groups on the N-terminal tails of histones resulting in the opening of the chromatin leading to euchromatin (10). TIP60 is also capable of acetylating non-histone proteins such as p53 and ATM allowing their activation (11-13). Many studies have s...

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Section: Methodsmentioning

confidence: 99%

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

Idrissou

Boisnier

Sánchez

et al. 2020

Cancer Genomics Proteomics

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“…A ChIP-seq study indicated that H3K36me3 was commonly found in HER2 positive breast cancer and both H3K4me3 and H3K79me2 were overexpressed in TNBC cell lines (Xi et al, 2018). A further study has accessed the relationship between the SIRT1, H3k4ac, H3k9ac, and H4k16ac in different subtypes of breast cancer and found that SIRT1 is upregulated in luminal and HER2-enriched subtypes and significant downregulation in TNBC subtype while H3k4ac, H3k9ac, and H4k16ac were significantly reduced in luminal and HER2-enriched subtypes and relatively upregulated in TNBC subtype (Rifai et al, 2018). Meanwhile, the histone variants including GH2AX, MACROH2A.1, and H2Bub1 and histone chaperones such as APLF and HJURP were identified as the potential epigenetic biomarkers targeting specific subtypes of breast cancer (Nandy et al, 2020)…”

Section: Insight Into the Subtype-specific Associations Between Histomentioning

confidence: 99%

Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis

et al. 2020

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Metastasis is a complex process that involved in various genetic and epigenetic alterations during the progression of breast cancer. Recent evidences have indicated that the mutation in the genome sequence may not be the key factor for increasing metastatic potential. Epigenetic changes were revealed to be important for metastatic phenotypes transition with the development in understanding the epigenetic basis of breast cancer. Herein, we aim to present the potential epigenetic drivers that induce dysregulation of genes related to breast tumor growth and metastasis, with a particular focus on histone modification including histone acetylation and methylation. The pervasive role of major histone modification enzymes in cancer metastasis such as histone acetyltransferases (HAT), histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and so on are demonstrated and further discussed. In addition, we summarize the recent advances of next-generation sequencing technologies and microfluidic-based devices for enhancing the study of epigenomic landscapes of breast cancer. This feature also introduces several important biotechnologists for identifying robust epigenetic biomarkers and enabling the translation of epigenetic analyses to the clinic. In summary, a comprehensive understanding of epigenetic determinants in metastasis will offer new insights of breast cancer progression and can be achieved in the near future with the development of innovative epigenomic mapping tools.

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“…HDAC SIRT1 embodies these properties, and orchestrates the regulation of multiple cancer-related genes through histone deacetylation. Indeed, SIRT1 contributes to the epigenetic silencing by deacetylating H3 and H4 acetylated markers such as histones H3 lysine 4 (H3K4) [ 40 ], lysine 56 (H3K56) [ 41 ], lysine 9 (H3K9), lysine 14 (H3K14), and histone H4 lysine 16 (H4K16) [ 42 , 43 ]. In breast cancer, SIRT1-dependent epigenetic silencing of both oncogenes and TSGs is reported.…”

Section: Sirt1-dependent Epigenetic Silencing Via Histone Modificamentioning

confidence: 99%

“…Furthermore, we revealed that SIRT1 deficiency is associated with substantial induction of acetylated markers on six breast cancer-related gene promoters: AR , BRCA1 , ERS1 , ERS2 , EZH2 , and EP300 , suggesting an active role of SIRT1 in regulating the expression of these genes in BC. We concluded that SIRT1 differential epigenetic regulation in breast cancer is predominantly governed by gene type and molecular subtype [ 40 , 47 ]. Other than BC, the duality of SIRT1 epigenetic regulation was also highlighted in colorectal cancer [ 48 ].…”

Section: Sirt1-dependent Epigenetic Silencing Via Histone Modificamentioning

confidence: 99%

Breaking down the Contradictory Roles of Histone Deacetylase SIRT1 in Human Breast Cancer

Rifaï

Idrissou

Penault‐Llorca

et al. 2018

Cancers

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Breast cancer (BC) is the most common type of cancer in women worldwide; it is a multifactorial genetic disease. Acetylation and deacetylation are major post-translational protein modifications that regulate gene expression and the activity of a myriad of oncoproteins. Aberrant deacetylase activity can promote or suppress tumorigenesis and cancer metastasis in different types of human cancers, including breast cancer. Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC) that deacetylates both histone and non-histone targets. The often-described ‘regulator of regulators’ is deeply implicated in apoptosis, gene regulation, genome maintenance, DNA repair, aging, and cancer development. However, despite the accumulated studies over the past decade, the role of SIRT1 in human breast cancer remains a subject of debate and controversy. The ambiguity surrounding the implications of SIRT1 in breast tumorigenesis stems from the discrepancy between studies, which have shown both tumor-suppressive and promoting functions of SIRT1. Furthermore, studies have shown that SIRT1 deficiency promotes or suppresses tumors in breast cancer, making it an attractive therapeutic target in cancer treatment. This review provides a comprehensive examination of the various implications of SIRT1 in breast cancer development and metastasis. We will also discuss the mechanisms underlying the conflicting roles of SIRT1, as well as its selective modulators, in breast carcinogenesis.

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SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human breast cancer

Cited by 47 publications

References 53 publications

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

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

Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis

Breaking down the Contradictory Roles of Histone Deacetylase SIRT1 in Human Breast Cancer

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