scholarly journals Genome-wide Mapping of the Coactivator Ada2p Yields Insight into the Functional Roles of SAGA/ADA Complex inCandida albicans

2009 ◽  
Vol 20 (9) ◽  
pp. 2389-2400 ◽  
Author(s):  
Adnane Sellam ◽  
Christopher Askew ◽  
Elias Epp ◽  
Hugo Lavoie ◽  
Malcolm Whiteway ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Target Genes ◽  
Transferase Activity ◽  
Histone Acetyl Transferase ◽  
Functional Roles ◽  
Cellular Processes ◽  
Oxidative Resistance ◽  
Genome Wide ◽  
Insight Into

The SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation, is widely conserved throughout eukaryotes, and analysis of the Candida albicans genome identifies the components of this complex in the fungal pathogen. We investigated the multiple functions of SAGA/ADA in C. albicans by determining the genome-wide occupancy of Ada2p using chromatin immunoprecipitation (ChIP). Ada2p is recruited to 200 promoters upstream of genes involved in different stress-response functions and metabolic processes. Phenotypic and transcriptomic analysis of ada2 mutant showed that Ada2p is required for the responses to oxidative stress, as well as to treatments with tunicamycin and fluconazole. Ada2p recruitment to the promoters of oxidative resistance genes is mediated by the transcription factor Cap1p, and coactivator function were also established for Gal4p, which recruits Ada2p to the promoters of glycolysis and pyruvate metabolism genes. Cooccupancy of Ada2p and the drug resistance regulator Mrr1p on the promoters of core resistance genes characterizing drug resistance in clinical strains was also demonstrated. Ada2p recruitment to the promoters of these genes were shown to be completely dependent on Mrr1p. Furthermore, ADA2 deletion causes a decrease in H3K9 acetylation levels of target genes, thus illustrating its importance for histone acetyl transferase activity.

scholarly journals Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

2016 ◽  
Author(s):  
Bony De Kumar ◽  
Hugo J. Parker ◽  
Ariel Paulson ◽  
Mark E. Parrish ◽  
Irina Pushel ◽  
...  
Keyword(s):  
Es Cells ◽  
Hox Proteins ◽  
Binding Motifs ◽  
Functional Roles ◽  
Regulatory Interactions ◽  
Mouse Es Cells ◽  
Genome Wide ◽  
A Genome ◽  
Combinatorial Interactions ◽  
Insight Into

AbstractHoxa1 has diverse functional roles in differentiation and development. We have identified and characterized properties of regions bound by Hoxa1 on a genome-wide basis in differentiating mouse ES cells. Hoxa1 bound regions are enriched for clusters of consensus binding motifs for Hox, Pbx and Meis and many display co-occupancy of Pbx and Meis. Pbx and Meis are members of the TALE family and genome-wide analysis of multiple TALE members (Pbx, Meis, TGIF, Prep1 and Prep2) show that nearly all Hoxa1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins defines distinct classes of Hoxa1 targets and indicates a role as cofactors in modulating the specificity of Hox proteins. We also discovered extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes. This study provides new insight into a regulatory network involving combinatorial interactions between Hoxa1 and TALE proteins.

scholarly journals New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System

2002 ◽  
Vol 22 (8) ◽  
pp. 2642-2649 ◽  
Author(s):  
Stéphane Le Crom ◽  
Frédéric Devaux ◽  
Philippe Marc ◽  
Xiaoting Zhang ◽  
W. Scott Moye-Rowley ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcription Factor ◽  
Binding Site ◽  
Time Course ◽  
Target Genes ◽  
Regulation System ◽  
Dependent Manner ◽  
Pleiotropic Drug Resistance ◽  
Genome Wide

ABSTRACT Yrr1p is a recently described Zn2Cys6 transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

Hepatocyte nuclear factor-1α is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo

2006 ◽  
Vol 290 (5) ◽  
pp. G1016-G1024 ◽  
Author(s):  
Tjalling Bosse ◽  
Herbert M. van Wering ◽  
Marieke Gielen ◽  
Lauren N. Dowling ◽  
John J. Fialkovich ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Target Genes ◽  
Transferase Activity ◽  
Alternative Mechanism ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Wild Type ◽  
Histone Acetyl Transferase ◽  
Hepatocyte Nuclear Factor 1Α

Hepatocyte nuclear factor-1α (HNF-1α) is a modified homeodomain-containing transcription factor that has been implicated in the regulation of intestinal genes. To define the importance and underlying mechanism of HNF-1α for the regulation of intestinal gene expression in vivo, we analyzed the expression of the intestinal differentiation markers and putative HNF-1α targets lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) in hnf1α null mice. We found that in adult jejunum, LPH mRNA in hnf1α−/− mice was reduced 95% compared with wild-type controls ( P < 0.01, n = 4), whereas SI mRNA was virtually identical to that in wild-type mice. Furthermore, SI mRNA abundance was unchanged in the absence of HNF-1α along the length of the adult mouse small intestine as well as in newborn jejunum. We found that HNF-1α occupies the promoters of both the LPH and SI genes in vivo. However, in contrast to liver and pancreas, where HNF-1α regulates target genes by recruitment of histone acetyl transferase activity to the promoter, the histone acetylation state of the LPH and SI promoters was not affected by the presence or absence of HNF-1α. Finally, we showed that a subset of hypothesized intestinal target genes is regulated by HNF-1α in vivo and that this regulation occurs in a defined tissue-specific and developmental context. These data indicate that HNF-1α is an activator of a subset of intestinal genes and induces these genes through an alternative mechanism in which it is dispensable for chromatin remodeling.

MicroRNA 299-3p modulates replicative senescence in endothelial cells

2013 ◽  
Vol 45 (7) ◽  
pp. 256-267 ◽  
Author(s):  
Hui-Lan Jong ◽  
Mohd Rais Mustafa ◽  
Paul M. Vanhoutte ◽  
Sazaly AbuBakar ◽  
Pooi-Fong Wong
Keyword(s):  
Endothelial Cells ◽  
Target Genes ◽  
Replicative Senescence ◽  
Umbilical Vein ◽  
Gene Profiling ◽  
Cellular Processes ◽  
Migration Capacity ◽  
Umbilical Vein Endothelial Cells ◽  
Insight Into

MicroRNAs (miRNAs) regulate various cellular processes. While several genes associated with replicative senescence have been described in endothelial cells, miRNAs that regulate these genes remain largely unknown. The present study was designed to identify miRNAs associated with replicative senescence and their target genes in human umbilical vein endothelial cells (HUVECs). An integrated miRNA and gene profiling approach revealed that hsa-miR-299-3p is upregulated in senescent HUVECs compared with the young cells, and one of its target genes could be IGF1. IGF1 was upregulated in senescent compared with young HUVECs, and knockdown of hsa-miR-299-3p dose-dependently increased the mRNA expression of IGF1, more significantly observed in the presenescent cells ( passage 19) compared with the senescent cells ( passage 25). Knockdown of hsa-miR-299-3p also resulted in significant reduction in the percentage of cells positively stained for senescence-associated β-galactosidase and increases in cell viability measured by MTT assay but marginal increases in cell proliferation and cell migration capacity measured by real-time growth kinetics analysis. Moreover, knockdown of hsa-miR-299-3p also increased proliferation of cells treated with H2O2 to induce senescence. These findings suggest that hsa-miR-299-3p may delay or protect against replicative senescence by improving the metabolic activity of the senesced cells but does not stimulate growth of the remaining cells in senescent cultures. Hence, these findings provide an early insight into the role of hsa-miR-299-3p in the modulation of replicative senescence in HUVECs.

scholarly journals Serotonin and Melatonin Biosynthesis in Plants: Genome-Wide Identification of the Genes and Their Expression Reveal a Conserved Role in Stress and Development

2021 ◽  
Vol 22 (20) ◽  
pp. 11034
Author(s):  
Bidisha Bhowal ◽  
Annapurna Bhattacharjee ◽  
Kavita Goswami ◽  
Neeti Sanan-Mishra ◽  
Sneh L. Singla-Pareek ◽  
...  
Keyword(s):  
Target Genes ◽  
Functional Characterization ◽  
Gene Families ◽  
Pcr Analysis ◽  
Tryptophan Decarboxylase ◽  
Cellular Processes ◽  
Genome Wide ◽  
A Genome ◽  
Suitable Target

Serotonin (Ser) and melatonin (Mel) serve as master regulators of plant growth and development by influencing diverse cellular processes. The enzymes namely, tryptophan decarboxylase (TDC) and tryptamine 5-hydroxylase (T5H) catalyse the formation of Ser from tryptophan. Subsequently, serotonin N-acetyl transferase (SNAT) and acetyl-serotonin methyltransferase (ASMT) form Mel from Ser. Plant genomes harbour multiple genes for each of these four enzymes, all of which have not been identified. Therefore, to delineate information regarding these four gene families, we carried out a genome-wide analysis of the genes involved in Ser and Mel biosynthesis in Arabidopsis, tomato, rice and sorghum. Phylogenetic analysis unravelled distinct evolutionary relationships among these genes from different plants. Interestingly, no gene family except ASMTs showed monocot- or dicot-specific clustering of respective proteins. Further, we observed tissue-specific, developmental and stress/hormone-mediated variations in the expression of the four gene families. The light/dark cycle also affected their expression in agreement with our quantitative reverse transcriptase-PCR (qRT-PCR) analysis. Importantly, we found that miRNAs (miR6249a and miR-1846e) regulated the expression of Ser and Mel biosynthesis under light and stress by influencing the expression of OsTDC5 and OsASMT18, respectively. Thus, this study may provide opportunities for functional characterization of suitable target genes of the Ser and Mel pathway to decipher their exact roles in plant physiology.

scholarly journals The VELVET Complex in the Gray Mold Fungus Botrytis cinerea: Impact of BcLAE1 on Differentiation, Secondary Metabolism, and Virulence

2015 ◽  
Vol 28 (6) ◽  
pp. 659-674 ◽  
Author(s):  
Julia Schumacher ◽  
Adeline Simon ◽  
Kim C. Cohrs ◽  
Stefanie Traeger ◽  
Antoine Porquier ◽  
...  
Keyword(s):  
Botrytis Cinerea ◽  
Natural Variation ◽  
Target Genes ◽  
Gray Mold ◽  
Carbohydrate Active Enzymes ◽  
Genome Wide ◽  
Mold Fungus ◽  
Velvet Complex ◽  
Genome Wide Expression ◽  
Insight Into

Botrytis cinerea, the gray mold fungus, is an important plant pathogen. Field populations are characterized by variability with regard to morphology, the mode of reproduction (conidiation or sclerotia formation), the spectrum of secondary metabolites (SM), and virulence. Natural variation in bcvel1 encoding the ortholog of Aspergillus nidulans VeA, a member of the VELVET complex, was previously shown to affect light-dependent differentiation, the formation of oxalic acid (OA), and virulence. To gain broader insight into the B. cinerea VELVET complex, an ortholog of A. nidulans LaeA, BcLAE1, a putative interaction partner of BcVEL1, was studied. BcVEL1 but not its truncated versions interacts with BcLAE1 and BcVEL2 (VelB ortholog). In accordance with the expected common as well as specific functions of BcVEL1 and BcLAE1, the deletions of both genes result in similar though not identical phenotypes. Both mutants lost the ability to produce OA, to colonize the host tissue, and to form sclerotia. However, mutants differ with regard to aerial hyphae and conidia formation. Genome-wide expression analyses revealed that BcVEL1 and BcLAE1 have common and distinct target genes. Some of the genes that are underexpressed in both mutants, e.g., those encoding SM-related enzymes, proteases, and carbohydrate-active enzymes, may account for their reduced virulence.

scholarly journals Identification of genome-wide alternative splicing events in sequential, isogenic clinical isolates of Candida albicans reveals a mechanism important for drug resistance and tolerance to cellular stress

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Suraya Muzafar ◽  
Neeraj Chauhan ◽  
Ravi Datta Sharma ◽  
Rajendra Prasad
Keyword(s):  
Drug Resistance ◽  
Candida Albicans ◽  
Alternative Splicing ◽  
Differential Expression ◽  
Single Gene ◽  
Antifungal Drugs ◽  
Protein Isoforms ◽  
Gene Splicing ◽  
Cellular Processes ◽  
Genome Wide

Alternative gene splicing (AS) is a process by which a single gene can give rise to different protein isoforms, generating proteome diversity. Despite recent advances in our understanding of AS in basic cellular processes, the role of AS in drug resistance and fungal pathogenesis is poorly understood. In Candida albicans, approximately 6% of the genes contain introns. Considering this low and random distribution of introns, we focused our study on alternative splicing (AS) and its impact on the development of drug resistance, an area largely unexplored in this yeast. We performed comparative RNA sequencing of sequential isogenic azole sensitive and resistant isolates of C. albicans. The analysis revealed differential expression of splice junctions/isoforms in 14 genes, between the drug sensitive and resistant isolates. Furthermore, C. albicans WT cells exposed to antifungal drugs, heat stress or metal deficiency also showed differential expression of isoforms for the genes undergoing AS. In this study we present data on the effect of AS on the function of SOD3. The C. albicans SOD3 has a single intron and is important for the removal of superoxide radicals. The overexpression of the two isoforms of SOD3 in its null background highlighted importance of spliced isoform in complementing the susceptibility to menadione. However, the two isoforms did not differ in rescuing the susceptibility of sod3Δ/Δto Amphotericin B. Collectively, these data suggest that AS may be a novel mechanism in C. albicans for stress adaptation and overcoming drug resistance.

scholarly journals Comparative genomics reveals high rates of horizontal transfer and strong purifying selection on rhizobial symbiosis genes

2021 ◽  
Vol 288 (1942) ◽  
pp. 20201804
Author(s):  
Brendan Epstein ◽  
Peter Tiffin
Keyword(s):  
Positive Selection ◽  
Horizontal Transfer ◽  
Purifying Selection ◽  
Comparative Genomic ◽  
N Fixation ◽  
Functional Roles ◽  
Genome Wide ◽  
Rhizobial Symbiosis ◽  
Legume Symbiosis ◽  
Insight Into

Horizontal transfer (HT) alters the repertoire of symbiosis genes in rhizobial genomes and may play an important role in the on-going evolution of the rhizobia–legume symbiosis. To gain insight into the extent of HT of symbiosis genes with different functional roles (nodulation, N-fixation, host benefit and rhizobial fitness), we conducted comparative genomic and selection analyses of the full-genome sequences from 27 rhizobial genomes. We find that symbiosis genes experience high rates of HT among rhizobial lineages but also bear signatures of purifying selection (low Ka : Ks). HT and purifying selection appear to be particularly strong in genes involved in initiating the symbiosis (e.g. nodulation) and in genome-wide association candidates for mediating benefits provided to the host. These patterns are consistent with rhizobia adapting to the host environment through the loss and gain of symbiosis genes, but not with host-imposed positive selection driving divergence of symbiosis genes through recurring bouts of positive selection.

scholarly journals PEREGRINE: A genome-wide prediction of enhancer to gene relationships supported by experimental evidence

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243791
Author(s):  
Caitlin Mills ◽  
Anushya Muruganujan ◽  
Dustin Ebert ◽  
Crystal N. Marconett ◽  
Juan Pablo Lewinger ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Specific Gene ◽  
Web Interface ◽  
Protein Coding ◽  
Cellular Processes ◽  
Genome Wide ◽  
A Genome ◽  
Dna Elements ◽  
Cell Type Specific

Enhancers are powerful and versatile agents of cell-type specific gene regulation, which are thought to play key roles in human disease. Enhancers are short DNA elements that function primarily as clusters of transcription factor binding sites that are spatially coordinated to regulate expression of one or more specific target genes. These regulatory connections between enhancers and target genes can therefore be characterized as enhancer-gene links that can affect development, disease, and homeostatic cellular processes. Despite their implication in disease and the establishment of cell identity during development, most enhancer-gene links remain unknown. Here we introduce a new, publicly accessible database of predicted enhancer-gene links, PEREGRINE. The PEREGRINE human enhancer-gene links interactive web interface incorporates publicly available experimental data from ChIA-PET, eQTL, and Hi-C assays across 78 cell and tissue types to link 449,627 enhancers to 17,643 protein-coding genes. These enhancer-gene links are made available through the new Enhancer module of the PANTHER database and website where the user may easily access the evidence for each enhancer-gene link, as well as query by target gene and enhancer location.

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