• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.3785-3792
• /
• 2015

The CCAAT/enhancer-binding protein-alpha (CEBPA) is a transcriptional factor that plays a crucial role in the control of proliferation and differentiation of myeloid precursors. This gene was recognized as the target of genetic alterations and were associated with clinical complexity among AML. We here analyze the frequency and types of CEBPA mutations and polymorphisms in a de novo AML patients from South India and tried to find out associations of these variations with different clinical parameters and the prognostic significance in AML. Study was carried out in 248 de novo AML patients, cytogenetic analysis was performed from the bone marrow samples and was karyotyped. PCR-SSCP analysis and sequencing was performed for the detection of CEBPA gene variations. All the statistical analysis was performed using SPSS 17 (statistical package for social sciences) software. Pearson Chi-square test, Mann-Whitney U test, Kaplan-Meier survival analysis and log rank tests were performed. CEBPA mutations were detected in 18% and CEBPA polymorphisms were detected in 18.9% of AML cases studied. Most of the mutations occured at the C terminal region. Polymorphisms were detected in both N and C terminal region. with most common being, c.584_589dup ACCCGC and c.690G>T. A significant association was not observed for the mutation and polymorphism with respect to clinical and laboratory parameters. Survival advantage was observed for the mutated cases compared to non mutated cases, especially for the normal karyotype groups. Polymorphisms has no effect on the survival pattern of AML patients. CEBPA mutation and polymorphisms were observed with similar frequency and was identified in all the FAB subtypes as well as in cytogenetic risk groups in our study population, but CEBPA mutations alone confer a prognostic value for NK AML patients.

• Development and Reproduction
• /
• v.26 no.2
• /
• pp.49-58
• /
• 2022

The differentiation and development of preadipocyte into mature adipocyte are regulated by transcription factors, such as CCAAT enhancer binding protein (Cebp) gene family and sterol regulatory element binding transcription factor 1 (Srebp1). Steroid hormones give influences on the development and function of adipocyte. The present research examined expression patterns of CCAAT enhancer binding protein alpha (Cebpa), CCAAT enhancer binding protein beta (Cebpb), CCAAT enhancer binding protein gamma (Cebpg), sterol regulatory element binding transcription factor 1 (Srebp1), androgen receptor (Ar), and estrogen receptors (Esr) among different epididymal fat parts during postnatal period by quantitative real-time polymerase chain reaction. In the distal epididymal fat, expression of Cebpa, Cebpb, Cebpg, Srebp1, Ar, and Esr2 was increased until 12 months of age, while expression of Esr1 was decreased at 5 months of age and was not detectable after 8 months of age. In the proximal epididymal fat, transcript levels of Cebps and Srebp1 were increased at 8 months of age, followed by decreases of Cebpb and Cebpg transcript levels at 12 months of age. An additional increase of Srebp1 expression was observed at 12 months of age. Expression of Ar and Esr2 were increased until 8 months of age, followed by a drop of Ar expression level at 12 months of age. Expression pattern of Esr1 was similar to that in the distal epididymal fat. In the tail epididymal fat, expression of Cebpa, Cebpg, Srebp1, Ar, and Esr2 was increased with age. Esr1 was not detectable at all. The highest level of Cebpb was observed at 8 months of age. These data suggest the possibility of developmental and functional differentiation among the epididymal fat parts.

• Journal of Animal Science and Technology
• /
• v.58 no.4
• /
• pp.14.1-14.9
• /
• 2016

Background: Peroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer binding protein alpha (CEBPA) and retinoid X receptor alpha (RXRA) are nuclear transcription factors that play important roles in regulation of adipogenesis and fat deposition. The objectives of this study were to characterise the variability of these three candidate genes in a mixed sample panel composed of several cattle breeds with different meat quality, validate single nucleotide polymorphisms (SNPs) in a local crossbred population (Angus - Hereford - Limousin) and evaluate their effects on meat quality traits (backfat thickness, intramuscular fat content and fatty acid composition), supporting the association tests with bioinformatic predictive studies. Results: Globally, nine SNPs were detected in the PPARG and CEBPA genes within our mixed panel, including a novel SNP in the latter. Three of these nine, along with seven other SNPs selected from the Single Nucleotide Polymorphism database (SNPdb), including SNPs in the RXRA gene, were validated in the crossbred population (N = 260). After validation, five of these SNPs were evaluated for genotype effects on fatty acid content and composition. Significant effects were observed on backfat thickness and different fatty acid contents (P < 0.05). Some of these SNPs caused slight differences in mRNA structure stability and/or putative binding sites for proteins. Conclusions: PPARG and CEBPA showed low to moderate variability in our sample panel. Variations in these genes, along with RXRA, may explain part of the genetic variation in fat content and composition. Our results may contribute to knowledge about genetic variation in meat quality traits in cattle and should be evaluated in larger independent populations.

• Journal of Ginseng Research
• /
• v.42 no.3
• /
• pp.312-319
• /
• 2018

Background: Previous studies have shown that both ginseng root and ginseng berry exhibit antiobesity and antidiabetic effects. However, a direct comparison of the efficacy and mechanisms between the root and the berry after oral administration remains to be illuminated. Methods: In this study, we observed the effects of fermented ginseng root (FGR) and fermented ginseng berry (FGB) on obesity and lipid metabolism in high-fat diet induced obese mice. Results: FGR and FGB significantly inhibited the activity of pancreatic lipase in vitro. Both FGR and FGB significantly suppressed weight gain and excess food intake and improved hypercholesterolemia and fatty liver, while only FGR significantly attenuated hyperglycemia and insulin resistance. Both FGR and FGB significantly inhibited the mRNA expression of Ldlr and Acsl1 while FGR also significantly inhibited expression of Cebpa and Dgat2 in liver. FGR significantly decreased the epididymal fat weight of mice while FGB significantly inhibited the mRNA expression of genes Cebpa, Fas, Hsl, Il1b, and Il6 in adipose tissue. Conclusion: Saponin from both FGR and FGB had a beneficial effect on high-fat diet-induced obesity. Compared to FGB, FGR exhibited more potent antihyperglycemic and antiobesity effect. However, only FGB significantly inhibited mRNA expression of inflammatory markers such as interleukins $1{\beta}$ and 6 in adipose tissue.

• Genomics & Informatics
• /
• v.11 no.1
• /
• pp.24-33
• /
• 2013

We had analyzed 10 exome sequencing data and single nucleotide polymorphism chips for blood cancer provided by the PGM21 (The National Project for Personalized Genomic Medicine) Award program. We had removed sample G06 because the pair is not correct and G10 because of possible contamination. In-house software somatic copy-number and heterozygosity alteration estimation (SCHALE) was used to detect one loss of heterozygosity region in G05. We had discovered 27 functionally important mutations. Network and pathway analyses gave us clues that NPM1, GATA2, and CEBPA were major driver genes. By comparing with previous somatic mutation profiles, we had concluded that the provided data originated from acute myeloid leukemia. Protein structure modeling showed that somatic mutations in IDH2, RASGEF1B, and MSH4 can affect protein structures.

• Genomics & Informatics
• /
• v.17 no.1
• /
• pp.8.1-8.10
• /
• 2019

Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, $NF-{\kappa}B$, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5341-5344
• /
• 2013

Objectives: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). Methods: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. Results: From age group 10-19 years to age group ${\geq}60$ years, the percentage of LC decreased from $67.0{\pm}18.4%$ to $49.0{\pm}25.1%$ (F=2.353, P=0.041). LC percentage was higher in patients with balanced karyotypes ($65.7{\pm}22.4%$), than those with unbalanced karyotypes ($46.0{\pm}26.6%$) (u=3.444, P=0.001) or a normal karyotype ($49.9{\pm}22.1%$) (u=5.093, P<0.001). Patients with FLT3-ITD ($64.3{\pm}19.5%$) had higher LC percentages compared with those without ($54.2{\pm}24.3%$) (u=2.794, P=0.007). Conclusions: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML.

• BMB Reports
• /
• v.49 no.8
• /
• pp.401-402
• /
• 2016

S6K1 is a key regulator of cell growth, cell size, and metabolism. Although the role of cytosolic S6K1 in cellular processes is well established, the function of S6K1 in the nucleus remains poorly understood. Our recent study has revealed that S6K1 is translocated into the nucleus upon adipogenic stimulus where it directly binds to and phosphorylates H2B at serine 36. Such phosphorylation promotes EZH2 recruitment and subsequent histone H3K27 trimethylation on the promoter of its target genes including Wnt6, Wnt10a, and Wnt10b, leading to repression of their expression. S6K1-mediated suppression of Wnt genes facilitates adipogenic differentiation through the expression of adipogenic transcription factors PPARγ and Cebpa. White adipose tissues from S6K1-deficient mice consistently exhibit marked reduction in H2BS36 phosphorylation (H2BS36p) and H3K27 trimethylation (H3K27me3), leading to enhanced expression of Wnt genes. In addition, expression levels of H2BS36p and H3K27me3 are highly elevated in white adipose tissues from mice fed on high-fat diet or from obese humans. These findings describe a novel role of S6K1 as a transcriptional regulator controlling an epigenetic network initiated by phosphorylation of H2B and trimethylation of H3, thus shutting off Wnt gene expression in early adipogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.2
• /
• pp.895-898
• /
• 2014

Objectives: The present study aimed to examine the cytogenetic and genetic mutation features of acute myeloid leukemia (AML) in elderly Chinese patients. Methods: A retrospective analysis of cytogenetics and genetic mutations was performed in 113 cases (age range 50-82 years) with de novo AML. Results: The most frequent cytogenetic abnormality was t (15;17) (q22;q21), detected in 10.0% (n = 9) of successfully analyzed cases, followed by t (8;21) (q22;q22) in 8.89% (n = 8), and complex karyotypes in 5.56% (n = 5). Those with complex karyotypes included 4 cases (4.44%) of monosomal karyotypes. The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 27.4% (31/113), 14.5% (16/110), 5.88% (6/102), and 23.3% (7/30), respectively. The complete remission rates of patients in low, intermediate, and high risk groups were 37.5%, 48.6%, and 33.3%, respectively (${\chi}^2$ = 0.704, P = 0.703) based on risk stratification. Conclusion: Cytogenetics and genetic mutations alone may not be sufficient to evaluate the prognoses of elderly AML patients. The search for a novel model that would enable a more comprehensive evaluation of this population is therefore imperative.

• Journal of Life Science
• /
• v.30 no.8
• /
• pp.713-721
• /
• 2020

Adipogenesis as a model system is needed to understand the molecular mechanisms of human adipocyte biology and the pathogenesis of obesity, diabetes, and other metabolic syndromes. Many relevant studies have been conducted with a focus on gene expression regulation and intracellular signaling relating to Peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are master adipogenic transcription factors. However, epigenome regulation of adipogenesis by epigenomic modifiers or histone mutations is not fully understood. Histone methylation is one of the major epigenetic modifications on gene expression in mammals, and histone H3 lysine methylation (H3Kme) in particular implicates cell differentiation during various tissue and organ development. During adipogenesis, cell type-specific enhancers are marked by histone H3K4me1 with the active enhancer mark H3K27ac. Mixed-lineage leukemia 4 (MLL4) is a major H3K4 mono-methyltransferase on the adipogenic enhancers of PPARγ and C/EBPα loci. Thus, MLL4 is an important epigenomic modifier for adipogenesis. The repressive mark H3K27me3 is mediated by the enzymatic subunit Enhancer zeste homolog 2 (EZH2) of the polycomb repressive complex 2. EZH2-mediated H3K27 tri-methylation on the Wnt gene increases adipogenesis because WNT signaling is a negative regulator of adipogenesis. This review summarizes current knowledge about the epigenomic regulation of adipogenesis by histone H3 lysine methylation which fundamentally regulates gene expression.