M. Olsson, K. Hultman, S. Dunoyer-Geindre, M. Curtis, R. Faull, E. Kruithof, C. Jern
{"title":"Epigenetic Regulation of Tissue-Type Plasminogen Activator in Human Brain Tissue and Brain-Derived Cells","authors":"M. Olsson, K. Hultman, S. Dunoyer-Geindre, M. Curtis, R. Faull, E. Kruithof, C. Jern","doi":"10.4137/GRSB.S30241","DOIUrl":"https://doi.org/10.4137/GRSB.S30241","url":null,"abstract":"The serine protease tissue-type plasminogen activator (t-PA) is involved in both vital physiological brain processes, such as synaptic plasticity, and pathophysiological conditions, such as neurodegeneration and ischemic stroke. Recent data suggest that epigenetic mechanisms play an important role in the regulation of t-PA in human endothelial cells. However, there are limited data on epigenetic regulation of t-PA in human brain-derived cells. We demonstrate that treatment of cultured human neurons and human astrocytes with the histone deacetylase inhibitors trichostatin A (TSA) and MS-275 resulted in a two- to threefold increase in t-PA mRNA and protein expression levels. Next, we performed a chromatin immunoprecipitation assay on treated astrocytes with antibodies directed against acetylated histones H3 and H4 (both markers of gene activation). Treatment with MS-275 and TSA for 24 hours resulted in a significant increase in H3 acetylation, which could explain the observed increase in t-PA gene activity after the inhibition of histone deacety-lation. Furthermore, DNA methylation analysis of cultured human neurons and astrocytes, as well as human postmortem brain tissue, revealed a stretch of unmethylated CpG dinucleotides in the proximal t-PA promoter, whereas more upstream CpGs were highly methylated. Taken together, these results implicate involvement of epigenetic mechanisms in the regulation of t-PA expression in the human brain.","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"10 1","pages":"9 - 13"},"PeriodicalIF":0.0,"publicationDate":"2016-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S30241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70703081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Congjun Li, Robert W. Li, R. Baldwin, L. Blomberg, Sitao Wu, Weizhong Li
{"title":"Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate-Induced Histone Modification","authors":"Congjun Li, Robert W. Li, R. Baldwin, L. Blomberg, Sitao Wu, Weizhong Li","doi":"10.4137/GRSB.S35607","DOIUrl":"https://doi.org/10.4137/GRSB.S35607","url":null,"abstract":"Butyrate is a nutritional element with strong epigenetic regulatory activity as a histone deacetylase inhibitor. Based on the analysis of differentially expressed genes in the bovine epithelial cells using RNA sequencing technology, a set of unique genes that are activated only after butyrate treatment were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network, using Ingenuity Pathways Analysis, indicated that these genes activated by butyrate treatment are related to major cellular functions, including cell morphological changes, cell cycle arrest, and apoptosis. Our results offered insight into the butyrate-induced transcriptomic changes and will accelerate our discerning of the molecular fundamentals of epigenomic regulation.","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"10 1","pages":"1 - 8"},"PeriodicalIF":0.0,"publicationDate":"2016-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S35607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70702966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biochemical Analysis of Genome Functions Using Locus-Specific Chromatin Immunoprecipitation Technologies","authors":"T. Fujita, H. Fujii","doi":"10.4137/GRSB.S32520","DOIUrl":"https://doi.org/10.4137/GRSB.S32520","url":null,"abstract":"To isolate specific genomic regions that retain their molecular interactions, allowing direct identification of chromatin-bound molecules, we developed two locus-specific chromatin immunoprecipitation (locus-specific ChIP) technologies, insertional ChIP (iChIP) and engineered DNA-binding molecule-mediated ChIP (enChIP) using the clustered regularly interspaced short palindromic repeats (CRISPR) system or transcription activator-like (TAL) proteins. Essentially, a locus-specific ChIP consists of locus-tagging and affinity purification and can be combined with downstream analyses to identify molecules associated with the target genomic regions. In this review, we discuss the applications of locus-specific ChIP to analyze the genome functions, including transcription and epigenetic regulation.","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"14 1","pages":"1 - 9"},"PeriodicalIF":0.0,"publicationDate":"2016-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S32520","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70703085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"tRNA-Derived Short Non-coding RNA as Interacting Partners of Argonaute Proteins.","authors":"Megumi Shigematsu, Yohei Kirino","doi":"10.4137/GRSB.S29411","DOIUrl":"https://doi.org/10.4137/GRSB.S29411","url":null,"abstract":"<p><p>The advent of next-generation sequencing technologies has not only accelerated findings on various novel non-coding RNA (ncRNA) species but also led to the revision of the biological significance and versatility of fundamental RNA species with canonical function, such as transfer RNAs (tRNAs). Although tRNAs are best known as adapter components of translational machinery, recent studies suggest that tRNAs are not always end products but can further serve as a source for short ncRNAs. In many organisms, various tRNA-derived ncRNA species are produced from mature tRNAs or their precursor transcripts as functional molecules involved in various biological processes beyond translation. In this review, we focus on the tRNA-derived ncRNAs associated with Argonaute proteins and summarize recent studies on their conceivable biogenesis factors and on their emerging roles in gene expression regulation as regulatory RNAs. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"9 ","pages":"27-33"},"PeriodicalIF":0.0,"publicationDate":"2015-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S29411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34199841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bai Xue, Jing Nie, Xi Wang, Debra C DuBois, William J Jusko, Richard R Almon
{"title":"Effects of High Fat Feeding on Adipose Tissue Gene Expression in Diabetic Goto-Kakizaki Rats.","authors":"Bai Xue, Jing Nie, Xi Wang, Debra C DuBois, William J Jusko, Richard R Almon","doi":"10.4137/GRSB.S25172","DOIUrl":"https://doi.org/10.4137/GRSB.S25172","url":null,"abstract":"<p><p>Development and progression of type 2 diabetes is a complex interaction between genetics and environmental influences. High dietary fat is one environmental factor that is conducive to the development of insulin-resistant diabetes. In the present report, we compare the responses of lean poly-genic, diabetic Goto-Kakizaki (GK) rats to those of control Wistar-Kyoto (WKY) rats fed a high fat diet from weaning to 20 weeks of age. This comparison included a wide array of physiological measurements along with gene expression profiling of abdominal adipose tissue using Affymetrix gene array chips. Animals of both strains fed a high fat diet or a normal diet were sacrificed at 4, 8, 12, 16, and 20 weeks for this comparison. The microarray analysis revealed that the two strains developed different adaptations to increased dietary fat. WKY rats decrease fatty acid synthesis and lipogenic processes whereas GK rats increase lipid elimination. However, on both diets the major differences between the two strains remained essentially the same. Specifically relative to the WKY strain, the GK strain showed lipoatrophy, chronic inflammation, and insulin resistance. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"9 ","pages":"15-26"},"PeriodicalIF":0.0,"publicationDate":"2015-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S25172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34019993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brendan D Stamper, Michael L Garcia, Duy Q Nguyen, Richard P Beyer, Theo K Bammler, Frederico M Farin, Terrance J Kavanagh, Sidney D Nelson
{"title":"p53 Contributes to Differentiating Gene Expression Following Exposure to Acetaminophen and Its Less Hepatotoxic Regioisomer Both In Vitro and In Vivo.","authors":"Brendan D Stamper, Michael L Garcia, Duy Q Nguyen, Richard P Beyer, Theo K Bammler, Frederico M Farin, Terrance J Kavanagh, Sidney D Nelson","doi":"10.4137/GRSB.S25388","DOIUrl":"https://doi.org/10.4137/GRSB.S25388","url":null,"abstract":"<p><p>The goal of the present study was to compare hepatic toxicogenomic signatures across in vitro and in vivo mouse models following exposure to acetaminophen (APAP) or its relatively nontoxic regioisomer 3'-hydroxyacetanilide (AMAP). Two different Affymetrix microarray platforms and one Agilent Oligonucleotide microarray were utilized. APAP and AMAP treatments resulted in significant and large changes in gene expression that were quite disparate, and likely related to their different toxicologic profiles. Ten transcripts, all of which have been implicated in p53 signaling, were identified as differentially regulated at all time-points following APAP and AMAP treatments across multiple microarray platforms. Protein-level quantification of p53 activity aligned with results from the transcriptomic analysis, thus supporting the implicated mechanism of APAP-induced toxicity. Therefore, the results of this study provide good evidence that APAP-induced p53 phosphorylation and an altered p53-driven transcriptional response are fundamental steps in APAP-induced toxicity. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"9 ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S25388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33373385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arafat Rahman Oany, Shah Adil Ishtiyaq Ahmad, Km Kaderi Kibria, Mohammad Uzzal Hossain, Tahmina Pervin Jyoti
{"title":"A Hypothetical Protein of Alteromonas macleodii AltDE1 (amad1_06475) Predicted to be a Cold-Shock Protein with RNA Chaperone Activity.","authors":"Arafat Rahman Oany, Shah Adil Ishtiyaq Ahmad, Km Kaderi Kibria, Mohammad Uzzal Hossain, Tahmina Pervin Jyoti","doi":"10.4137/GRSB.S20802","DOIUrl":"https://doi.org/10.4137/GRSB.S20802","url":null,"abstract":"<p><p>Alteromonas macleodii AltDE1 is a deep sea protobacteria that is distinct from the surface isolates of the same species. This study was designed to elucidate the biological function of amad1_06475, a hypothetical protein of A. macleodii AltDE1. The 70 residues protein sequence showed considerable homology with cold-shock proteins (CSPs) and RNA chaperones from different organisms. Multiple sequence alignment further supported the presence of conserved csp domain on the protein sequence. The three-dimensional structure of the protein was also determined, and verified by PROCHECK, Verify3D, and QMEAN programs. The predicted structure contained five anti-parallel β-strands and RNA-binding motifs, which are characteristic features of prokaryotic CSPs. Finally, the binding of a thymidine-rich oligonucleotide and a single uracil molecule in the active site of the protein further strengthens our prediction about the function of amad1_06475 as a CSP and thereby acting as a RNA chaperone. The binding was performed by molecular docking tools and was compared with similar binding of 3PF5 (PDB) and 2HAX (PDB), major CSPs of Bacillus subtilis and Bacillus caldolyticus, respectively. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"8 ","pages":"141-7"},"PeriodicalIF":0.0,"publicationDate":"2014-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S20802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32962752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun-Ichi Satoh, Naohiro Asahina, Shouta Kitano, Yoshihiro Kino
{"title":"A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia.","authors":"Jun-Ichi Satoh, Naohiro Asahina, Shouta Kitano, Yoshihiro Kino","doi":"10.4137/GRSB.S19711","DOIUrl":"https://doi.org/10.4137/GRSB.S19711","url":null,"abstract":"<p><p>Microglia are resident mononuclear phagocytes that play a principal role in the maintenance of normal tissue homeostasis in the central nervous system (CNS). Microglia, rapidly activated in response to proinflammatory stimuli, are accumulated in brain lesions of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The E26 transformation-specific (ETS) family transcription factor PU.1/Spi1 acts as a master regulator of myeloid and lymphoid development. PU.1-deficient mice show a complete loss of microglia, indicating that PU.1 plays a pivotal role in microgliogenesis. However, the comprehensive profile of PU.1/Spi1 target genes in microglia remains unknown. By analyzing a chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) dataset numbered SRP036026 with the Strand NGS program, we identified 5,264 Spi1 target protein-coding genes in BV2 mouse microglial cells. They included Spi1, Irf8, Runx1, Csf1r, Csf1, Il34, Aif1 (Iba1), Cx3cr1, Trem2, and Tyrobp. By motif analysis, we found that the PU-box consensus sequences were accumulated in the genomic regions surrounding ChIP-Seq peaks. By using pathway analysis tools of bioinformatics, we found that ChIP-Seq-based Spi1 target genes show a significant relationship with diverse pathways essential for normal function of monocytes/macrophages, such as endocytosis, Fc receptor-mediated phagocytosis, and lysosomal degradation. These results suggest that PU.1/Spi1 plays a crucial role in regulation of the genes relevant to specialized functions of microglia. Therefore, aberrant regulation of PU.1 target genes might contribute to the development of neurodegenerative diseases with accumulation of activated microglia. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"8 ","pages":"127-39"},"PeriodicalIF":0.0,"publicationDate":"2014-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S19711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32962751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanya J Thakur, Aldiouma Guindo, Londyn R Cullifer, Yi Li, Ikhide G Imumorin, Dapa A Diallo, Bolaji N Thomas
{"title":"Endothelin-1 but not Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with Sickle Cell Disease in Africa.","authors":"Tanya J Thakur, Aldiouma Guindo, Londyn R Cullifer, Yi Li, Ikhide G Imumorin, Dapa A Diallo, Bolaji N Thomas","doi":"10.4137/GRSB.S14836","DOIUrl":"https://doi.org/10.4137/GRSB.S14836","url":null,"abstract":"<p><p>Sickle cell disease shows marked variability in severity and pathophysiology among individuals, probably linked to differential expression of various adhesion molecules. In this study, we investigated the differential distribution, genomic diversity and haplotype frequency of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) polymorphisms, recently implicated as important in modification of disease severity. One hundred and forty five sickle cell disease patients (HbSS) and 244 adult and pediatric controls, without sickle cell disease (HbAA), were recruited from Mali. Genotypic analysis of the functionally significant eNOS variants (T786C, G894T and intron 4) and endothelin-1 (G5665T) was carried out with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our results show that the wild type alleles are the most frequent for all eNOS variants between cases and controls. Allelic and genotypic frequencies of eNOS polymorphic groups are not significantly different between cases and controls (P > 0.05). In addition, there is no association between eNOS variants and sickle cell disease, contrary to published reports. On the other hand, we report that endothelin-1 (G5665T) mutant variant had the lowest allelic frequency, and is significantly associated with sickle cell disease in Africa (P < 0.05). Similarly, haplotype frequencies were the same between cases and controls, except for the haplotype combining all mutant variants (T, C, 4a; P = 0.01). eNOS polymorphic variants are less frequent, with no significance with sickle cell disease in Africa. On the other hand, endothelin-1 is associated with sickle cell disease, and has the capacity to redefine pathophysiology and possibly serve as modulator of disease phenotype. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"8 ","pages":"119-26"},"PeriodicalIF":0.0,"publicationDate":"2014-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S14836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32425481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Tjärnlund-Wolf, Karin Hultman, Fredrik Blomstrand, Michael Nilsson, Robert L Medcalf, Christina Jern
{"title":"Species-Specific Regulation of t-PA and PAI-1 Gene Expression in Human and Rat Astrocytes.","authors":"Anna Tjärnlund-Wolf, Karin Hultman, Fredrik Blomstrand, Michael Nilsson, Robert L Medcalf, Christina Jern","doi":"10.4137/GRSB.S13387","DOIUrl":"https://doi.org/10.4137/GRSB.S13387","url":null,"abstract":"<p><p>In recent years, the role and physiological regulation of the serine protease tissue-type plasminogen activator (t-PA) and its inhibitors, including plasminogen activator inhibitor type-1 (PAI-1), in the brain have received much attention. However, as studies focusing these issues are difficult to perform in humans, a great majority of the studies conducted to date have utilized rodent in vivo and/or in vitro models. In view of the species-specific structural differences present in both the t-PA and the PAI-1 promoters, we have compared the response of these genes in astrocytes of rat and human origin. We reveal marked quantitative and qualitative species-specific differences in gene induction following treatment with various physiological and pathological stimuli. Thus, our findings are of importance for the interpretation of previous and future results related to t-PA and PAI-1 expression. </p>","PeriodicalId":73138,"journal":{"name":"Gene regulation and systems biology","volume":"8 ","pages":"113-8"},"PeriodicalIF":0.0,"publicationDate":"2014-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/GRSB.S13387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32363563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}