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Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells.

ABSTRACT: Histone gene expression is tightly controlled during cell cycle. The epigenetic mechanisms underlying this regulation remain to be fully elucidated. Pygopus 2 (Pygo2) is a context-dependent co-activator of Wnt/?-catenin signaling and a chromatin effector that participates in histone modification. In this study, we show that Pygo2 is required for the optimal expression of multiple classes of histone genes in cultured human mammary epithelial cells. Using chromatin immunoprecipitation assay, we demonstrate that Pygo2 directly occupies the promoters of multiple histone genes and enhances the acetylation of lysine 56 in histone H3 (H3K56Ac), previously shown to facilitate yeast histone gene transcription at these promoters. Moreover, we report reduced global levels of H3K56Ac in Pygo2-depleted cells that occur in a cell cycle-independent manner. Together, our data uncover a novel regulator of mammalian histone gene expression that may act in part via modifying H3K56Ac.

SUBMITTER: Gu B

PROVIDER: S-EPMC3272233 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells.

Gu Bingnan B Watanabe Kazuhide K Dai Xing X

Cell cycle (Georgetown, Tex.) 20120101 1

Histone gene expression is tightly controlled during cell cycle. The epigenetic mechanisms underlying this regulation remain to be fully elucidated. Pygopus 2 (Pygo2) is a context-dependent co-activator of Wnt/β-catenin signaling and a chromatin effector that participates in histone modification. In this study, we show that Pygo2 is required for the optimal expression of multiple classes of histone genes in cultured human mammary epithelial cells. Using chromatin immunoprecipitation assay, we de ...[more]

PMID: 22186018

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Project description:BackgroundIn practical production, dairy cows are frequently exposed to bacterial endotoxin (lipopolysaccharide, LPS) when they are subjected to high-concentrate diets, poor hygienic environments, as well as mastitis and metritis. Histone acetylation is an important epigenetic control of DNA transcription and a higher histone acetylation is associated with facilitated transcription. LPS might reduce histone acetylation in the mammary epithelial cells, resulting in lower transcription and mRNA expression of lactation-related genes. This study was conducted to investigate the effect of LPS on histone acetylation in bovine mammary epithelial cells and the efficacy of sodium butyrate (SB) in suppressing the endotoxin-induced adverse effect. Firstly, the bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng), and the acetylation levels of histones H3 and H4 as well as the histone deacetylase (HDAC) activity were measured. Secondly, the MAC-T cells were treated for 48 h as follows: control, LPS (100 EU/mL), and LPS (100 EU/mL) plus SB (10 mmol/L), and the acetylation levels of histones H3 and H4 as well as milk gene mRNA expressions were determined.ResultsThe results showed that HDAC activity increased linearly with increasing LPS doses (P < 0.01). The histone H3 acetylation levels were significantly reduced by LPS, while the histone H4 acetylation levels were not affected by LPS (P > 0.05). Sodium butyrate, an inhibitor of HDAC, effectively suppressed the endotoxin-induced decline of histone H3 acetylation (P < 0.05). As a result, SB significantly enhanced the mRNA expression of lactation-related genes (P < 0.05).ConclusionsThe results suggest one of the adverse effects of LPS on the lactation of bovine mammary gland epithelial cells was due to decreasing histone H3 acetylation through increasing HDAC activity, whereas the endotoxin-induced adverse effects were effectively suppressed by SB.

Project description:Histone acetylation and deacetylation are essential for gene regulation and have been implicated in the regulation of plant hormone responses. Many studies have indicated the role of histone acetylation in ethylene signaling; however, few studies have investigated how ethylene signaling regulates the genomic landscape of chromatin states. Recently, we found that ethylene can specifically elevate histone H3K14 acetylation and the non-canonical histone H3K23 acetylation in etiolated seedlings and the gene activation is positively associated with the elevation of H3K14Ac and H3K23Ac in response to ethylene. To assess the role of H3K9, H3K14, and H3K23 histone modifications in the ethylene response, we examined how ethylene regulates histone acetylation and the transcriptome at global level and in ethylene regulated genes both in wild type (Col-0) and ein2-5 seedlings.Our results revealed that H3K9Ac, H3K14Ac, and H3K23Ac are preferentially enriched around the transcription start sites and are positively correlated with gene expression levels in Col-0 and ein2-5 seedlings both with and without ethylene treatment. In the absence of ethylene, no combinatorial effect of H3K9Ac, H3K14Ac, and H3K23Ac on gene expression was detected. In the presence of ethylene, however, combined enrichment of the three histone acetylation marks was associated with high gene expression levels, and this ethylene-induced change was EIN2 dependent. In addition, we found that ethylene-regulated genes are expressed at medium or high levels, and a group of ethylene regulated genes are marked by either one of H3K9Ac, H3K14Ac or H3K23Ac. In this group of genes, the levels of H3K9Ac were altered by ethylene, but in the absence of ethylene the levels of H3K9Ac and peak breadths are distinguished in up- and down- regulated genes. In the presence of ethylene, the changes in the peak breadths and levels of H3K14Ac and H3K23Ac are required for the alteration of gene expressions.Our study reveals that the plant hormone ethylene induces combinatorial effects of H3K9Ac, K14Ac and K23Ac histone acetylation in gene expression genome widely. Further, for a group of ethylene regulated genes, in the absence of ethylene the levels and the covered breadths of H3K9Ac are the preexist markers for distinguishing up- and down- regulated genes, the change in the peak breadths and levels of H3K14Ac and H3K23Ac are required for the alteration of gene expression in the presence of ethylene.

Dataset Information

Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells.

Publications

Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells.

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