Polyamine analogues: potent inducers of nucleosomal array oligomerization and inhibitors of yeast cell growth

Carruthers, Lenny M.; Marton, Laurence J.; Peterson, Craig L.

doi:10.1042/bj20061347

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…Gilmour and colleagues (Hobbs and Gilmour 2000; Hobbs et al 2002; Hobbs et al 2003; Hobbs et al 2006; Wei et al 2007) have demonstrated that changes in polyamines can lead to significant changes in chromatin acetylation. More importantly, the oligoamines have been shown to be potent inducers of nucleosomal array oligomerization (Carruthers et al 2007), thus emphasizing their potential for direct effects on chromatin in addition to inhibition of LSD1. However, additional studies are required to determine the precise basis of the differential effects of these two polyamine analogues.…”

Section: Discussionmentioning

confidence: 99%

Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells

et al. 2011

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Aberrant epigenetic repression of gene expression has been implicated in most cancers, including breast cancer. The nuclear amine oxidase, lysine-specific demethylase 1 (LSD1) has the ability to broadly repress gene expression by removing the activating mono- and di-methylation marks at the lysine 4 residue of histone 3 (H3K4me1 & me2). Additionally, LSD1 is highly expressed in estrogen receptor α negative (ER−) breast cancer cells. Since epigenetic marks are reversible, they make attractive therapeutic targets. Here we examine the effects of polyamine analogue inhibitors of LSD1 on gene expression, with the goal of targeting LSD1 as a therapeutic modality in the treatment of breast cancer. Exposure of the ER-negative human breast cancer cells, MDA-MB-231, to the LSD1 inhibitors, 2d or PG11144, significantly increases global H3K4me1 and H3K4me2, and alters gene expression. Array analysis indicated that 98 (75 up and 23 down) and 477 (237 up and 240 down) genes changed expression by at least 1.5-fold or greater after treatment with 2d and PG11144, respectively. The expression of twelve up-regulated genes by 2d and fourteen up-regulated genes by PG11144 was validated by quantitative RT-PCR. Quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated that up-regulated gene expression by polyamine analogues is associated with increase of the active histone marks H3K4me1, H3K4me2 and H3K9ac, and decrease of the repressive histone marks H3K9me2 and H3K27me3, in the promoter regions of the relevant target genes. These data indicate that the pharmacologic inhibition of LSD1 can effectively alter gene expression and that this therapeutic strategy has potential.

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Section: Discussionmentioning

confidence: 99%

Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells

et al. 2011

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“…One of the most common inhibitors of ODC used in cancer therapy is difluo‐methylornithine (Meyskens and Gerner ). However, tumor cells have the ability to absorb extracellular amines from food or amines produced by gastrointestinal bacteria, and therefore, the therapy was not effective (Seiler ,b; Carruthers and others ). Nevertheless, preliminary clinical studies have shown that reducing the dietary intake of polyamines and decreasing the production of polyamines by intestinal microflora are beneficial for the quality of patients´ life and pain management (Cipolla and others ).…”

Section: Putrescine and Its Effects On The Human Bodymentioning

confidence: 99%

Formation, Degradation, and Detoxification of Putrescine by Foodborne Bacteria: A Review

Wunderlichová

Buňková

Koutný

et al. 2014

Comp Rev Food Sci Food Safe

142

118

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Biogenic amines (BAs) represent a considerable toxicological risk in some food products. Putrescine is one of the most common BAs in food. Its increased occurrence in food may lead to alimentary poisoning, due to enhancement of the toxic effects of other BAs, and also to lower quality of food, this amine is potentially carcinogenic. Increased occurrence of putrescine in food is mainly due to the bacterial metabolism of the Gram-negative as well as Gram-positive bacteria present. The bacterial metabolism of putrescine is very specific due to its complexity (in comparison with the metabolism of other BAs). There are 3 distinct known pathways leading toward the formation of putrescine, in some splices involving up to 6 different enzymes. The existence of more metabolic pathways and the possibility of their simultaneous use by different bacteria complicate the specification of the best conditions for food production and storage, which could lead to a lower content of putrescine. This review provides a summary of the existing knowledge about putrescine production and detection (mainly detection of specific genes for different enzymes using polymerase chain reaction) in both starter and contaminating microorganisms. Thus, this comprehensive review gives a useful overview for further research.

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“…Proteins were resolved by SDS-PAGE, and histones expression was analyzed by Western blots. Chicken erythrocyte histone octamers and nucleosomal array preparations (45) were kindly provided by Craig Peterson (University of Massachusetts School of Medicine, Worcester, MA).…”

Section: Methodsmentioning

confidence: 99%

Role of Jade-1 in the Histone Acetyltransferase (HAT) HBO1 Complex

Foy

Song

Chitalia

et al. 2008

Journal of Biological Chemistry

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Regulation of global chromatin acetylation is important for chromatin remodeling. A small family of Jade proteins includes Jade-1L, Jade-2, and Jade-3, each bearing two mid-molecule tandem plant homology domain (PHD) zinc fingers. We previously demonstrated that the short isoform of Jade-1L protein, Jade-1, is associated with endogenous histone acetyltransferase (HAT) activity. It has been found that Jade-1L/2/3 proteins co-purify with a novel HAT complex, consisting of HBO1, ING4/5, and Eaf6. We investigated a role for Jade-1/1L in the HBO1 complex. When overexpressed individually, neither Jade-1/1L nor HBO1 affected histone acetylation. However, co-expression of Jade-1/1L and HBO1 increased acetylation of the bulk of endogenous histone H4 in epithelial cells in a synergistic manner, suggesting that Jade1/1L positively regulates HBO1 HAT activity. Conversely, small interfering RNA-mediated depletion of endogenous Jade resulted in reduced levels of H4 acetylation. Moreover, HBO1-mediated H4 acetylation activity was enhanced severalfold by the presence of Jade-1/1L in vitro. The removal of PHD fingers affected neither binding nor mutual Jade-1-HBO1 stabilization but completely abrogated the synergistic Jade-1/ 1L-and HBO1-mediated histone H4 acetylation in live cells and in vitro with reconstituted oligonucleosome substrates. Therefore, PHDs are necessary for Jade-1/1L-induced acetylation of nucleosomal histones by HBO1. In contrast to Jade-1/1L, the PHD zinc finger protein ING4/5 failed to synergize with HBO1 to promote histone acetylation. The physical interaction of ING4/5 with HBO1 occurred in the presence of Jade-1L or Jade-3 but not with the Jade-1 short isoform. In summary, this study demonstrates that Jade-1/1L are crucial co-factors for HBO1-mediated histone H4 acetylation.Gene for apoptosis and differentiation-1, Jade-1 (PHF17), has been identified as a protein interacting with the von Hippel Lindau gene product by a yeast two-hybrid approach (1). The 509-amino acid Jade-1 protein contains one canonical Cys 4 HisCis 3 plant homology domain (PHD) 2 followed by a noncanonical extended PHD domain, which are zinc-binding motifs. Most PHD family proteins are localized to the cell nucleus and are associated with chromatin, chromatin-modifying enzymes, and transcription factors (2, 3). We recently reported that endogenous Jade-1 is localized to the cell nucleus and that ectopically expressed Jade-1 possesses intrinsic transcriptional activity (4). Most importantly, we demonstrated that Jade-1 can promote endogenous histone H4 acetylation by associating with a histone H4-specific endogenous HAT. Interestingly, the histone H4-specific HAT, TIP60, interacted with Jade-1 physically and functionally in vitro and in live cells.Gene data base analysis revealed two other Jade-1 homologs, Jade-2 (PHF15) and Jade-3 (PHF16). Jade-3 has been previously identified by screening genes induced by steroid hormones in breast cancer cells (5). Jade-1 mRNA gives rise to two protein products, the full-length Jade-1L consisting of ...

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Polyamine analogues: potent inducers of nucleosomal array oligomerization and inhibitors of yeast cell growth

Cited by 10 publications

References 33 publications

Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells

Polyamine analogs modulate gene expression by inhibiting lysine-specific demethylase 1 (LSD1) and altering chromatin structure in human breast cancer cells

Formation, Degradation, and Detoxification of Putrescine by Foodborne Bacteria: A Review

Role of Jade-1 in the Histone Acetyltransferase (HAT) HBO1 Complex

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