ABSTRACT
Histone post-translational modifications play important roles in transcriptional regulation. It is known that multiple histone modifications can act in a combinatorial manner. In this study, we investigated the effects of multiple histone modifications on expression levels of five gene categories (four kinds of pattern genes and non-pattern genes) in coding regions. The combinatorial patterns of modifications for the five gene categories were also studied in the regions. Our results indicated that the differences in the expression levels between any two gene categories were significant. There were some corresponding differences in multiple histone modification levels among the five gene categories. Multiple histone modifications jointly impacted expression levels of every gene category. Four mutual combinations of histone modifications were found and analyzed.
Subject(s)
Computational Biology/methods , Gene Expression Regulation , Histones/metabolism , Protein Processing, Post-Translational , Transcription Factors/metabolism , Histone Code , Histones/genetics , Humans , Transcription Factors/geneticsABSTRACT
Some genes tend to cluster and be co-expressed. Multiple factors affect gene co-expression. In this study, we investigated the relationships between multiple factors and the correlations of expression levels of neighboring genes, which were divided into four kinds of pattern genes and one type of non-pattern gene. Our results indicate that the correlation between expression levels of neighboring non-pattern genes is related to multiple factors with the exception of transcriptional orientations of neighboring genes. The correlation between expression levels of neighboring specific genes or neighboring repressed genes is likely to be dependent on the co-functions of neighboring genes. The correlation between expression levels of neighboring housekeeping genes is associated with histone modifications in intergenic regions.
Subject(s)
DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation , Histone Code , Acetylation , Animals , Gene Ontology , Humans , Multigene Family , TranscriptomeABSTRACT
Histone modification is an important subject of epigenetics that plays an intrinsic role in transcriptional regulation. It has been suggested that multiple histone modifications act in a combinatorial fashion to form a 'histone code'. In this study, the combinatorial patterns of histone modifications were studied by using a Bayesian network at the level of individual nucleosomes in S. cerevisiae. Our results indicated that there were 23 combinatorial patterns for 12 histone modifications investigated when a general Bayesian network was constructed. Meanwhile, different networks were also constructed for the genes with high transcript levels (H-network) and low transcript levels (L-network), respectively. Comparison among the general network, H-network and L-network illustrated four conserved combinations: H2BK16Ac â H3K4me3; H3K14Ac â H3K4me3; H2AK7Ac â H3K14Ac; and H4K12Ac â H3K18Ac. The detailed analysis for some combinations demonstrated that the combinations were ascribed to some histone-modifying enzymes.
Subject(s)
Histones/metabolism , Protein Processing, Post-Translational , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Epigenesis, Genetic , Gene Expression Regulation, Fungal , Histone Code , Histones/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/geneticsABSTRACT
OBJECTIVE: To investigate the effects of a Chinese herb Cordyceps sinensis (C. sinensis) extract on hypoxia-induced proliferation and the underlying mechanisms involved. METHODS: This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells (PASMCs) was measured using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen (PCNA), c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry. RESULTS: We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs. CONCLUSION: Our results indicated that C. sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle (S+G2/M) phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension.
