• Journal of the Korean Society of Food Science and Nutrition
• /
• v.46 no.2
• /
• pp.169-176
• /
• 2017

Non-alcoholic fatty liver disease (NAFLD) is caused by chronic lipid accumulation due to dysregulation of lipid metabolism in the liver, and it is associated with various human diseases such as obesity, dyslipidemia, hypertension, and diabetes. Histone acetylation is a representative epigenetic mechanism regulated by histone acetyltransferases (HATs) and deacetylases. We observed that tartary buckwheat sprout (TBS) suppressed lipid accumulation in HepG2 cells through its anti-HAT activity. We showed that TBS was a novel HAT inhibitor with specificity for the major HAT enzyme p300. Importantly, TBS reduced acetylation of total and histone proteins, H3K9, H3K36, and H4K8, resulting in decreased transcriptional activities of sterol regulatory element-binding protein 1c, ATP citrate lyase, and fatty acid synthase. These results suggest that TBS inhibits the NAFLD transcription-modulating activity of lipogenesis-related genes through modification of histone acetylation.

• Molecules and Cells
• /
• v.42 no.7
• /
• pp.530-545
• /
• 2019

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive $CD133^+/CD24^-$ cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

• The Plant Pathology Journal
• /
• v.36 no.4
• /
• pp.314-322
• /
• 2020

Interplay between histone acetylation and deacetylation is one of the key components in epigenetic regulation of transcription. Here we report the requirement of MoHDA1-mediated histone deacetylation during asexual development and pathogenesis for the rice blast fungus, Magnaporthe oryzae. Structural similarity and phylogenetic analysis suggested that MoHDA1 is an ortholog of Saccharomyces cerevisiae Hda1, which is a representative member of class II histone deacetylases. Targeted deletion of MoHDA1 caused a little decrease in radial growth and large reduction in asexual sporulation. Comparison of acetylation levels for H3K9 and H3K14 showed that lack of MoHDA1 gene led to significant increase in H3K9 and H3K14 acetylation level, compared to the wild-type and complementation strain, confirming that it is a bona fide histone deacetylase. Expression analysis on some of the key genes involved in asexual reproduction under sporulation-promoting condition showed almost no differences among strains, except for MoCON6 gene, which was up-regulated more than 6-fold in the mutant than wild-type. Although the deletion mutant displayed little defects in germination and subsequent appressorium formation, the mutant was compromised in its ability to cause disease. Wound-inoculation showed that the mutant is impaired in invasive growth as well. We found that the mutant was defective in appressorium-mediated penetration of host, but did not lose the ability to grow on the media containing H₂O₂. Taken together, our data suggest that MoHDA1-dependent histone deacetylation is important for efficient asexual development and infection of host plants in M. oryzae.

• Korean Journal of Microbiology
• /
• v.53 no.4
• /
• pp.286-291
• /
• 2017

In eukaryotic cells, histone modification is an important mechanism to regulate the chromatin structure. The methylation of the fourth lysine on histone H3 (H3K4) by Set1 complex is one of the various well-known histone modifications. Set1 complex has seven subunits including Swd2, which is known to be important for H2B ubiquitination dependent on H3K4 methylation. Swd2 was reported to regulate Set1's methyltransferase activity by binding to near RNA recognition motif (RRM) domain of Set1 and to act as a component of CPF (Cleavage and Polyadenylation Factors) complex involved in RNA 3' end processing. According to the recent reports, two functions of Swd2 work independently of each other and the lethality of Swd2 knockout strain was known to be caused by its function as a component of CPF complex. In this study, we found that Swd2 could influence the Set1's stability as well as histone methyltransferase activity through the association with RRM domain of Set1. Also, we found that ${\Delta}swd2$ mutant bearing truncated-Set1, which cannot interact with Swd2, lost its lethality and grew normally. These results suggest that the dual functions of Swd2 in H3K4 methylation and RNA 3' end processing are not independent in Saccharomyces cerevisiae.

• Genomics & Informatics
• /
• v.8 no.4
• /
• pp.201-205
• /
• 2010

The H1 histone family, member N, testis-specific (H1FNT) is exclusively expressed in the testis, and had its possible role for sperm chromatin formation. The purpose of this study is to investigate any genetic association of H1FNT gene with male infertility, especially at the promoter region. We examined the promoter single nucleotide polymorphisms (SNP) of H1FNT gene which is located within transcription factor binding site for its association with male infertility. The statistical analysis showed that the -1129A>T polymorphism was present at a statistically significance in male infertility (p=0.0059 and 0.0349 for hetero and risk type, respectively). The dual-luciferase promoter assay was performed to examine the polymorphic effect of this promoter SNP by the cloning of promoter region (1700bp fragment) into pGL3-basic vector. In our plasmid based reporter system, there is no big difference between wild and risk type. In conclusion, H1FNT -1129A>T promoter SNP is statistically significant with male infertility, especially with subfertile (non-azoospermia) group. Further analysis of its functional polymorphic effect in vivo may provide the biological significance of testis-specific histone with spermatogenesis.

• Food Science and Biotechnology
• /
• v.16 no.3
• /
• pp.457-462
• /
• 2007

Histone acetyltransferase (HAT) is a family of enzymes that regulate histone acetylation. Dysfunction of HAT plays a critical role in the development of cancer. Here we have screened the various plant extracts to find out the potent HAT inhibitors. The bellflower (Platycodon grandiflorum) root have exhibited approximately 30% of the inhibitory effects on HAT activity, especially p300 and CBP (CREB-binding protein) at the concentration of $100\;{\mu}g/mL$. The cell viability was decreased approximately 52% in LNCaP cell for 48 hr incubation. Furthermore, mRNA level of 3 androgen receptor target genes, PSA, NKX3.1, and TSC22 were decreased with bellflower root extract treatment ($100\;{\mu}g/mL$) in the presence of androgen. In ChIP assay, the acetylation of histone H3 and H4 in PSA promoter region was dramatically repressed by bellflower root treatment, but not TR target gene, Dl. Therefore, the potent HAT inhibitory effect of bellflower root led to the decreased transcription of AR target genes and prostate cancer cell growth with the repression of histone hyperacetylation.

• Korean Journal of Plant Resources
• /
• v.22 no.3
• /
• pp.203-208
• /
• 2009

Lunasin is a unique 43-amino acid peptide which has shown a chemopreventive in mammalian cells and in a skin cancer mouse model. In search for new sources of lunasin and the role of cereals in cancer prevention, we report here the properties of lunasin purified from millet. Stability of millet lunasin was measured by in vitro digestibility assay using pepsin and pancreatin. Inhibition of HAT (histone acetyltransferase) and nuclear localization in mammalian cells were used to measure lunasin bioactivity as the cancer chemopreventive agent. Lunasin present in millet crude protein was stable to pepsin and pancreatin in in vitro digestion and inhibited the activities of HATs. When added exogenously, lunasin purified from millet internalized in the nuclei of mouse fibroblast cells. On the base of this result, we conclude that lunasin in millet is bioactive and consumption of millet may play an important role on cancer prevention in millet-consuming populations.

• Animal cells and systems
• /
• v.16 no.4
• /
• pp.289-294
• /
• 2012

Histone methylation has diverse functions including transcriptional regulation via its lysine or arginine residue methylation. Studies indicate that deregulation of histone methylation is linked to human cancers including leukemia. Histone H3K27 methyltrnasferase response element II binding protein (RE-IIBP), as a transcriptional repressor to target gene IL-5, interacts with HDAC and is over-expressed in leukemia patient samples. In this study, we have identified that hematopoiesis-related genes GATA1 and HOXA9 are down-regulated by RE-IIBP in K562 and 293T cells. Transient reporter analysis revealed that GATA1 transcription was repressed by RE-IIBP. On the other hand, HOXA9 and PBX-related homeobox gene MEIS1 was up-regulated by RE-IIBP. These results suggest that RE-IIBP might have a role in hematopoiesis or leukemogenesis by regulating the transcription of target genes, possibly via its H3K27 methyltransferase activity.

• BMB Reports
• /
• v.31 no.5
• /
• pp.484-491
• /
• 1998

Acetylation of lysine residues within the aminoterminal domains of the core histones plays a critical role in chromatin assemhly as well as in regulation of gene expression. To study the biochemical function of histone acetylation, we have cloned a cDNA encoding the catalytic subunit of human histone acetyltransferase, Hat1. Analysis of the predicted amino acid sequence of human Hat1 revealed an open reading frame of 419 amino acids with a calculated molecular mass of 49.5 kDa and an isoelectric point of 5.5. The amino acid sequence of human Hat1 is homologous to those of known and putative Hat1 proteins from various species throughout the entire open reading frame. The recombinant human Hat1 protein expressed in bacteria possesses histone H4 acetyltransferase activity in vitro. Both RbAp46 and RbAp48, which participate in various processes of histone metabolism, enhance the histone acetyltransferase activity of the recombinant human Hat1, indicating that they are both able to functionally interact with the human Hat1 in vitro.

• Reproductive and Developmental Biology
• /
• v.38 no.4
• /
• pp.147-158
• /
• 2014

Differentiated nuclei can experimentally be returned to an undifferentiated embryonic status after nuclear transfer (NT) to unfertilized metaphase II (MII) oocytes. Nuclear reprogramming is triggered immediately after somatic cell nucleus transfer (SCNT) into recipient cytoplasm and this period is regarded as a key stage for optimizing reprogramming. In a recent study (Dai et al., 2010), use of m-carboxycinnamic acid bishydroxamide (CBHA) as a histone deacetylase inhibitor during the in vitro early culture of murine cloned embryos modifies the acetylation status of somatic nuclei and increases the developmental competence of SCNT embryos. Thus, we examined the effects of CBHA treatment on the in vitro preimplantation development of porcine SCNT embryos and on the acetylated status of histone H3K9 on cloned embryos at the zygote stage. We performed the three groups SCNT: SCNT (NT), CBHA treatment at the porcine fetus fibroblast cells (PFFs) used as donor cells prior to SCNT (CBHA-C) and CBHA treatment at the porcine SCNT embryos during the in vitro early culture after oocyte activation (CBHA-Z). The PFFs were treated with a $15{\mu}M$ of CBHA (8 h) for the early culture and the porcine cloned embryos were treated with a $100{\mu}M$ concentration of CBHA during the in vitro early culture (10 h). Cleavage rates and development to the blastocyst stage were assessed. No significant difference was observed the cleavage rate among the groups (82.6%, 76.4% and 82.2%, respectively). However, the development competence to the blastocyst stage was significantly increased in CBHA-Z embryos (22.7%) as compared to SCNT and CBHA-C embryos (8.6% and 4.1%)(p<0.05). Total cell numbers and viable cell numbers at the blastocyst stage of porcine SCNT embryos were increased in CBHA-Z embryos as compared to those in CBHA-C embryos (p<0.05). Signal level of histone acetylation (H3K9ac) at the zygote stage of SCNT was increased in CBHA-Z embryos as compared to SCNT and CBHA-C embryos. The results of the present study suggested that treatment with CBHA during the in vitro early culture (10 h) had significantly increased the developmental competence and histone acetylation level at the zygote stage.