Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; MCF-7 Cells ; N-Terminal Acetyltransferases/metabolism* ; Organoplatinum Compounds/pharmacology* ; Oxaliplatin/pharmacology* ; X-ray Repair Cross Complementing Protein 1

Histone acetylation is one of the epigenetic modifications. Histone acetylation, which is catalyzed by histone acetyltransferases and negatively regulated by histone deacetylases, plays an important role in a variety of cellular physiological and pathophysiological processes. Recent studies have shown that histone deacetylases are involved in a variety of pathophysiological responses to acute kidney injury, such as apoptosis, dedifferentiation, proliferation and regeneration. This article reviews the role and underlying mechanism of histone deacetylases in acute kidney injury induced by ischemia reperfusion, nephrotoxicants, sepsis and rhabdomyolysis.
Acetylation ; Acute Kidney Injury ; Histone Acetyltransferases/metabolism* ; Histone Deacetylases/metabolism* ; Humans ; Protein Processing, Post-Translational

In most insects, polyunsaturated fatty acids (PUFAs) are mainly polyunsaturated fatty acids with a carbon-chain length less than 18 carbon atoms, hardly any long-chain polyunsaturated fatty acids such as C20 and C22 that are more valuable and bioactive. This study, by using Drosophila melanogaster (Fruit fly) as a model organism, optimized the Δ6-fatty acid elongase enzyme Elovl5 gene from mice and transferred it to fruit flies for expression. Vectors containing Elovl5 gene were successfully injected into drosophila embryo through the microscopic injection. There were enhanced green fluorescent proteins expressed in the whole developmental stage of Drosophila be means of fluorescence microscope. At the same time, expression of Elovl5 gene significantly contributed to the transformation of fruit flies C18-polyunsaturated fatty acids in the body towards the biosynthesis of longer-chain polyunsaturated fatty acids. The transgenic fruit fly model rich in long-chain polyunsaturated fatty acids such as C20 and C22 were obtained, providing a basis for further research on biosynthesis of polyunsaturated fatty acids in fruit flies.
Acetyltransferases/genetics* ; Animals ; Drosophila melanogaster/genetics* ; Fatty Acid Elongases/metabolism* ; Fatty Acids/genetics* ; Gene Transfer Techniques ; Mice

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.
Acetylation ; Dietary Supplements ; Epigenomics ; Hep G2 Cells ; Histone Acetyltransferases ; Histones ; Lipid Metabolism ; Lipogenesis ; Liver ; Lysine ; Metabolic Diseases ; Non-alcoholic Fatty Liver Disease ; RNA, Messenger ; Sterol Regulatory Element Binding Protein 1

OBJECTIVE: This study aims to investigate the mechanism of K (lysine) acetyltransferase 2A (KAT2A) regulation and control on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). METHODS: The expression levels of KAT2A in PDLSCs were compared from each generation of the normal (H-PDLSCs) and periodontitis tissues (P-PDLSCs). The influences of KAT2A gene interference on the osteogenic differentiation of PDLSCs were also detected. In addition, the influences of the KAT2A gene interference to the canonical Wnt pathway and ligands were detected. The upstream and down-stream relationships between KAT2A and canonical Wnt pathway were also determined. RESULTS: The decreased expression of KAT2A in PDLSCs from the inflammatory tissue in each generation was compared with that in PDLSCs from the healthy tissue, and the difference was statistically significant (P<0.05). When the KAT2A gene was disrupted, the osteogenesis ability of PDLSC was declined, and the difference was statistically significant (P<0.05). The canonical Wnt pathway was activated, and the antagonist Dickkopf-1 (DKK-1) was reduced. After the DKK-1 addition, the osteogenic differentiation of the disturbed PDLSCs was recovered, and KAT2A was unaffected. CONCLUSIONS The KAT2A expression in PDLSCs was decreased because of perio-dontitis. The classical Wnt pathway was activated to inhibit the osteogenic differentiation of the cells.
Acetyltransferases ; Cell Differentiation ; Cells, Cultured ; Histone Acetyltransferases ; metabolism ; Humans ; Lysine ; Osteogenesis ; Periodontal Ligament ; metabolism ; Periodontitis ; metabolism ; Stem Cells ; Wnt Signaling Pathway

OBJECTIVE: To study the interactive regulatory effect of histone acetylation and methylation on cardiomyogenesis, and to provide a theoretical basis for the prevention and treatment of congenital heart disease. METHODS: A total of 24 Kunming mice were randomly divided into embryo day 14.5 (ED 14.5) group, embryo day 16.5 (ED 16.5) group, postnatal day 0.5 (PND 0.5) group, and postnatal day 7 (PND 7) group, with 6 mice in each group, and the heart tissue of fetal and neonatal mice was collected. Colorimetry was used to measure the activities of histone acetylases (HATs) and histone methyltransferases (HMTs) in the myocardium. Western blot was used to measure the expression of H3K9ac and H3K9me3 in the myocardium. RESULTS: Colorimetry showed that the activities of HATs and HMTs were higher before birth and were lower after birth. There was a significant difference in the activity of HATs in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 group (P<0.05), as well as between the PND 7 group and the ED 16.5 group (P<0.05). There was also a significant difference in the activity of HMTs in the myocardium between the PND 7 group and the ED 14.5 and ED 16.5 groups (P<0.05). Western blot showed higher expression of H3K9ac and H3K9me3 before birth and lower expression of H3K9ac and H3K9me3 after birth, and there were significant differences in the expression H3K9ac and H3K9me3 in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 and ED 16.5 groups (P<0.05). CONCLUSIONS The dynamic expression of HATs, HMTs, H3K9ac, and H3K9me3 is observed during cardiomyogenesis, suggesting that histone H3K9ac acetylation and histone H3K9me3 methylation mediated by HATs and HMTs may play a role in interactive regulation during cardiomyogenesis.
Acetylation ; Animals ; Histone Acetyltransferases ; Histones ; metabolism ; Methylation ; Mice ; Protein Processing, Post-Translational

UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination. However, TIP60 is destabilized in cancer cells. Depletion or inhibition of TIP60 disrupts the regulatory relationship between UHRF2, H3K9ac and H3K14ac. In summary, the findings suggest that UHRF2 mediated the post-translational modification of histones and the initiation and progression of cancer.
Cell Line ; Histone Acetyltransferases ; genetics ; metabolism ; Histones ; genetics ; metabolism ; Humans ; Lysine Acetyltransferase 5 ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasms ; genetics ; metabolism ; RING Finger Domains ; Ubiquitin-Protein Ligases ; genetics ; metabolism ; Ubiquitination

PURPOSE: The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters. MATERIALS AND METHODS: Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commercially available kits. Nuclear DNA integrity was also measured by TUNEL assay. RESULTS: The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r=-0.53, p<0.01). CONCLUSION: Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.
Acetylation ; Adult ; DNA Fragmentation ; Epigenesis, Genetic ; Histone Acetyltransferases/*metabolism ; Histones/*metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Protein Processing, Post-Translational ; Semen Analysis ; Spermatozoa/*metabolism

Glucose homeostasis is tightly controlled by the regulation of glucose production in the liver and glucose uptake into peripheral tissues, such as skeletal muscle and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly responsible for glucose production in the liver, which is essential for tissues, organs, and cells, such as skeletal muscle, the brain, and red blood cells. Hepatic gluconeogenesis is controlled in part by the concerted actions of transcriptional regulators. Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. Protein arginine methyltransferases (PRMTs) were recently added to the list of enzymes that are critical for regulating transcription in hepatic gluconeogenesis. In this review, we briefly discuss general aspects of PRMTs in the control of transcription. More specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of FoxO1- and CREB-dependent transcriptional events.
Acetyltransferases ; Adipose Tissue ; Arginine* ; Brain ; Erythrocytes ; Fasting ; Gluconeogenesis ; Glucose* ; Homeostasis ; Liver ; Metabolism* ; Methyltransferases* ; Muscle, Skeletal ; Phosphoric Monoester Hydrolases ; Phosphotransferases ; Protein-Arginine N-Methyltransferases ; Transcription Factors

OBJECTIVETo explore the role of histone H3 acetylation in cleft palate induced by 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice, and its mechanism.

METHODSOn gestation day 10 (GD10), 36 pregnant mice were randomly divided into two groups as the treated group(n = 18) and the control group( n = 18). The mice in the treated group received intragastric administration with TCDD 28 μg/kg, while the mice in the control group received equivalent corn oil. The pregnant mice were sacrificed on GD13. 5, GD14. 5 and GD15. 5, collecting fetal palates to determine the activities of histone acetyltransferases (HATs) by Colorimetric and the expression level of acetylated histone H3 (Acetylated histone H3, Ac-H3) by Western-blot.

RESULTSThe activity of HATs was 0.409 7 ± 0.0147, 0.522 3 ± 0.017 1 and 0.643 5 ± 0.013 9 in control group on GD13.5, GD14.5 and GD15.5; 0.865 0 ± 0.0129, 0.719 1 ± 0.017 8 and 0.551 2 ± 0.016 8 in TCDD group. The activity of HATs in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference between the two groups (t = - 56. 932, t = - 19. 516, P < 0.01); however, the activity of HATs in TCDD group was significantly lower than that in control group on GD15. 5 (t = 10. 382, P < 0.01). The expression level of Ac-H3 was 0.745 0 ± 0.113 5, 1.055 9 ± 0.249 4 and 1.795 5 ± 0.081 9 in control group on GD13. 5, GD14. 5 and GD15. 5; while 1.4490 ± 0. 1460, 1. 641 8 ± 0.099 7 and 1. 512 1 ± 0. 150 2 in TCDD group. The expression of Ac-H3 in TCDD group was higher than that in control group on GD13. 5, GD14. 5, showing significantly difference( t = -6. 593, -3. 779, P <0. 01, P <0.05) ; However, the expression of Ac-H3 in TCDD group was statistically lower than that in control group (t = 2. 870, P <0. 05).

CONCLUSIONThe acetylation of histone H3 was involved in the cleft palate of C57BL/6J mice induced by TCDD, which may be one of the mechanisms in TCDD-induced cleft palate.

Acetylation ; drug effects ; Acetyltransferases ; metabolism ; Animals ; Cleft Palate ; chemically induced ; metabolism ; Dioxins ; Female ; Fetus ; Histones ; metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; Pregnancy ; Random Allocation ; Teratogens