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Two Novel Transcriptional Regulators Are Essential for Infection-related Morphogenesis and Pathogenicity of the Rice Blast Fungus Magnaporthe oryzae  [PDF]
Xia Yan,Ya Li,Xiaofeng Yue,Congcong Wang,Yawei Que,Dandan Kong,Zhonghua Ma,Nicholas J. Talbot,Zhengyi Wang
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1002385
Abstract: The cyclic AMP-dependent protein kinase A signaling pathway plays a major role in regulating plant infection by the rice blast fungus Magnaporthe oryzae. Here, we report the identification of two novel genes, MoSOM1 and MoCDTF1, which were discovered in an insertional mutagenesis screen for non-pathogenic mutants of M. oryzae. MoSOM1 or MoCDTF1 are both necessary for development of spores and appressoria by M. oryzae and play roles in cell wall differentiation, regulating melanin pigmentation and cell surface hydrophobicity during spore formation. MoSom1 strongly interacts with MoStu1 (Mstu1), an APSES transcription factor protein, and with MoCdtf1, while also interacting more weakly with the catalytic subunit of protein kinase A (CpkA) in yeast two hybrid assays. Furthermore, the expression levels of MoSOM1 and MoCDTF1 were significantly reduced in both Δmac1 and ΔcpkA mutants, consistent with regulation by the cAMP/PKA signaling pathway. MoSom1-GFP and MoCdtf1-GFP fusion proteins localized to the nucleus of fungal cells. Site-directed mutagenesis confirmed that nuclear localization signal sequences in MoSom1 and MoCdtf1 are essential for their sub-cellular localization and biological functions. Transcriptional profiling revealed major changes in gene expression associated with loss of MoSOM1 during infection-related development. We conclude that MoSom1 and MoCdtf1 functions downstream of the cAMP/PKA signaling pathway and are novel transcriptional regulators associated with cellular differentiation during plant infection by the rice blast fungus.
The Lrp Family of Transcription Regulators in Archaea  [PDF]
Eveline Peeters,Daniel Charlier
Archaea , 2010, DOI: 10.1155/2010/750457
Abstract: Archaea possess a eukaryotic-type basal transcription apparatus that is regulated by bacteria-like transcription regulators. A universal and abundant family of transcription regulators are the bacterial/archaeal Lrp-like regulators. The Lrp family is one of the best studied regulator families in archaea, illustrated by investigations of proteins from the archaeal model organisms: Sulfolobus, Pyrococcus, Methanocaldococcus, and Halobacterium. These regulators are extremely versatile in their DNA-binding properties, response to effector molecules, and molecular regulatory mechanisms. Besides being involved in the regulation of the amino acid metabolism, they also regulate central metabolic processes. It appears that these regulatory proteins are also involved in large regulatory networks, because of hierarchical regulations and the possible combinatorial use of different Lrp-like proteins. Here, we discuss the recent developments in our understanding of this important class of regulators.
The Lrp Family of Transcription Regulators in Archaea  [PDF]
Eveline Peeters,Daniel Charlier
Archaea , 2010, DOI: 10.1155/2010/750457
Abstract: Archaea possess a eukaryotic-type basal transcription apparatus that is regulated by bacteria-like transcription regulators. A universal and abundant family of transcription regulators are the bacterial/archaeal Lrp-like regulators. The Lrp family is one of the best studied regulator families in archaea, illustrated by investigations of proteins from the archaeal model organisms: Sulfolobus, Pyrococcus, Methanocaldococcus, and Halobacterium. These regulators are extremely versatile in their DNA-binding properties, response to effector molecules, and molecular regulatory mechanisms. Besides being involved in the regulation of the amino acid metabolism, they also regulate central metabolic processes. It appears that these regulatory proteins are also involved in large regulatory networks, because of hierarchical regulations and the possible combinatorial use of different Lrp-like proteins. Here, we discuss the recent developments in our understanding of this important class of regulators. 1. Introduction The response and adaptation to environmental and nutritional changes, which is essential for the fitness and survival of microorganisms, is driven largely by regulation at the transcriptional level. In archaea, the vast majority of proteins that exert transcription regulation by binding the DNA and affecting gene expression are predicted to resemble bacterial classes of transcription regulators [1]. Almost 50% of all thus far identified regulators can be found in archaea and bacteria, while only 1.7% is common between archaea and eukaryotes [2]. Most of these predicted archaeal regulatory proteins possess a helix-turn-helix (HTH) DNA-binding motif, a typical bacterial motif. Intriguingly, archaea have a basal transcription machinery that is homologous to that of eukaryotes, albeit it being a simplified version, as is also the case for other information processes such as replication and translation [3–7]. Both cis and trans elements share homology with their eukaryotic counterparts. Cases in point are the main promoter elements TATA box and factor B recognition element (BRE) on the one hand, and the general transcription factors TATA-binding protein (TBP), transcription factor B (TFB), and the RNA polymerase (RNAP) on the other hand [3, 8]. The unique archaeal RNAP is most reminiscent of the eukaryotic RNAPII, having up to 13 subunits [9–11]. This peculiar hybrid situation raises the question as to how these bacterial-type regulators in archaeal organisms interact with the eukaryotic-like basal transcription machinery. This is especially true for
Inferring yeast cell cycle regulators and interactions using transcription factor activities
Young-Lyeol Yang, Jason Suen, Mark P Brynildsen, Simon J Galbraith, James C Liao
BMC Genomics , 2005, DOI: 10.1186/1471-2164-6-90
Abstract: Using gNCA, we determined 74 TFAs from both wild type and fkh1 fkh2 deletion mutant microarray data encompassing 1529 ORFs. We hypothesized that transcription factors participating in the cell cycle regulation exhibit cyclic activity profiles. This hypothesis was supported by the TFA profiles of known cell cycle factors and was used as a basis to uncover other potential cell cycle factors. By combining the results from both cluster analysis and periodicity analysis, we recovered nearly 90% of the known cell cycle regulators, and identified 5 putative cell cycle-related transcription factors (Dal81, Hap2, Hir2, Mss11, and Rlm1). In addition, by analyzing expression data from transcription factor knockout strains, we determined 3 verified (Ace2, Ndd1, and Swi5) and 4 putative interaction partners (Cha4, Hap2, Fhl1, and Rts2) of the forkhead transcription factors. Sensitivity of TFAs to connectivity errors was determined to provide confidence level of these predictions.By subjecting TFA profiles to analyses based upon physiological signatures we were able to identify cell cycle related transcription factors consistent with current literature, transcription factors with potential cell cycle dependent roles, and interactions between transcription factors.Transcription factor activities (TFAs) rather than levels of transcription factor expression mediate transcriptional regulations. Various post-transcriptional and post-translational modifications abolish significant correlations between TFAs and the level of transcription factor expression. Therefore, a strategy to determine the physiological functions and interactions of transcription factors based on the analysis of TFA profiles would be more fundamentally sound than one based on transcript levels per se. However, owing to post-translational modifications, TFAs are difficult to measure experimentally and therefore, many analyses infer TFAs by computational analysis of target gene expression levels either from single re
Extensive Polycistronism and Antisense Transcription in the Mammalian Hox Clusters  [PDF]
Ga?ll Mainguy, Jan Koster, Joost Woltering, Hans Jansen, Antony Durston
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000356
Abstract: The Hox clusters play a crucial role in body patterning during animal development. They encode both Hox transcription factor and micro-RNA genes that are activated in a precise temporal and spatial sequence that follows their chromosomal order. These remarkable collinear properties confer functional unit status for Hox clusters. We developed the TranscriptView platform to establish high resolution transcriptional profiling and report here that transcription in the Hox clusters is far more complex than previously described in both human and mouse. Unannotated transcripts can represent up to 60% of the total transcriptional output of a cluster. In particular, we identified 14 non-coding Transcriptional Units antisense to Hox genes, 10 of which (70%) have a detectable mouse homolog. Most of these Transcriptional Units in both human and mouse present conserved sizeable sequences (>40 bp) overlapping Hox transcripts, suggesting that these Hox antisense transcripts are functional. Hox clusters also display at least seven polycistronic clusters, i.e., different genes being co-transcribed on long isoforms (up to 30 kb). This work provides a reevaluated framework for understanding Hox gene function and dys-function. Such extensive transcriptions may provide a structural explanation for Hox clustering.
Eukaryotic transcription factors  [cached]
Thomas Eulgem
Genome Biology , 2001, DOI: 10.1186/gb-2001-2-2-reports0004
Abstract: Within the Arabidopsis genome, 1,533 genes were found to encode members of known transcription factor families, 45% of which are from families specific for plants. The fraction of transcription factor genes among all genes is slightly higher in Arabidopsis (5.9%) compared with Drosophila, C. elegans and yeast (4.5, 3.5 and 3.5%, respectively). A variety of prominent transcription factor families are present in all four species, including Myb, basic helix-loop-helix, basic leucine zipper, C2H2 zinc finger and homeodomain transcription factors. Except for the conserved DNA-binding domains, however, there are no significant similarities between members of the same transcription factor family from different kingdoms.Three types of evolutionary process appear to be mainly responsible for the observed differences in transcription factor complements: the generation of completely novel families; the specific amplification of families common to all three eukaryotic kingdoms; and domain shuffling, leading to new combinations of common transcription factor domains. As well as several small families, the large families of AP2/EREBP, NAC and WRKY transcription factors, consisting of 144, 109 and 72 members, respectively, are found exclusively in plants. In contrast, nuclear hormone receptors and GAL4-like C6 zinc finger proteins, which are strongly represented in animals and yeast, respectively, appear to be absent from plants. In plants, the Myb superfamily is strongly amplified, comprising 190 members. These regulators, which constitute the largest class of plant transcription factors, are only weakly represented in the other eukaryotic kingdoms. Exon shuffling has led to transcription factors unique to plants that contain both homeodomains and leucine zippers. In addition to these HD-ZIP proteins, leucine zippers can be found in the plant-specific WRKY factors as well as in basic leucine zippers, which are present in all three eukaryotic kingdoms.Supplementary data to Science
Transcription Factor Binding Site Analysis Identifies FOXO Transcription Factors as Regulators of the Cutaneous Wound Healing Process  [PDF]
Karl Markus Roupé, Srinivas Veerla, Joshua Olson, Erica L. Stone, Ole E. S?rensen, Stephen M. Hedrick, Victor Nizet
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089274
Abstract: The search for significantly overrepresented and co-occurring transcription factor binding sites in the promoter regions of the most differentially expressed genes in microarray data sets could be a powerful approach for finding key regulators of complex biological processes. To test this concept, two previously published independent data sets on wounded human epidermis were re-analyzed. The presence of co-occurring transcription factor binding sites for FOXO1, FOXO3 and FOXO4 in the majority of the promoter regions of the most significantly differentially expressed genes between non-wounded and wounded epidermis implied an important role for FOXO transcription factors during wound healing. Expression levels of FOXO transcription factors during wound healing in vivo in both human and mouse skin were analyzed and a decrease for all FOXOs in human wounded skin was observed, with FOXO3 having the highest expression level in non wounded skin. Impaired re-epithelialization was found in cultures of primary human keratinocytes expressing a constitutively active variant of FOXO3. Conversely knockdown of FOXO3 in keratinocytes had the opposite effect and in an in vivo mouse model with FOXO3 knockout mice we detected significantly accelerated wound healing. This article illustrates that the proposed approach is a viable method for identifying important regulators of complex biological processes using in vivo samples. FOXO3 has not previously been implicated as an important regulator of wound healing and its exact function in this process calls for further investigation.
Reverse Transcriptase and Cellular Factors: Regulators of HIV-1 Reverse Transcription  [PDF]
Kylie Warren,David Warrilow,Luke Meredith,David Harrich
Viruses , 2009, DOI: 10.3390/v1030873
Abstract: There is ample evidence that synthesis of HIV-1 proviral DNA from the viral RNA genome during reverse transcription requires host factors. However, only a few cellular proteins have been described in detail that affect reverse transcription and interact with reverse transcriptase (RT). HIV-1 integrase is an RT binding protein and a number of IN-binding proteins including INI1, components of the Sin3a complex, and Gemin2 affect reverse transcription. In addition, recent studies implicate the cellular proteins HuR, AKAP149, and DNA topoisomerase I in reverse transcription through an interaction with RT. In this review we will consider interactions of reverse transcription complex with viral and cellular factors and how they affect the reverse transcription process.
LAMMER Kinase LkhA Plays Multiple Roles in the Vegetative Growth and Asexual and Sexual Development of Aspergillus nidulans  [PDF]
Eun-Hye Kang, Ji-ae Kim, Hyun-Woo Oh, Hee-Moon Park
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058762
Abstract: LAMMER kinase plays pivotal roles in various physiological processes in eukaryotes; however, its function in filamentous fungi is not known. We performed molecular studies on the function of the Aspergillus nidulans LAMMER kinase, LkhA, and report its involvement in multiple developmental processes. The gene for LkhA was highly expressed during reproductive organ development, such as that of conidiophores and cleistothecia. During vegetative growth, the patterns of germ tube emergence and hyphal polarity were changed and septation was increased by lkhA deletion. Northern analyses showed that lkhA regulated the transcription of brlA, csnD, and ppoA, which supported the detrimental effect of lkhA-deletion on asexual and sexual differentiation. LkhA also affected expression of cyclin-dependent kinase NimXcdc2, a multiple cell cycle regulator, and StuA, an APSES family of fungal transcription factors that play pivotal roles in multiple differentiation processes. Here, for the first time, we present molecular evidence showing that LAMMER kinase is involved in A. nidulans development by modulating the expression of key regulators of developmental processes.
Extensive Modulation of the Transcription Factor Transcriptome during Somatic Embryogenesis in Arabidopsis thaliana  [PDF]
Marta Gliwicka, Katarzyna Nowak, Salma Balazadeh, Bernd Mueller-Roeber, Malgorzata D. Gaj
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069261
Abstract: Molecular mechanisms controlling plant totipotency are largely unknown and studies on somatic embryogenesis (SE), the process through which already differentiated cells reverse their developmental program and become embryogenic, provide a unique means for deciphering molecular mechanisms controlling developmental plasticity of somatic cells. Among various factors essential for embryogenic transition of somatic cells transcription factors (TFs), crucial regulators of genetic programs, are believed to play a central role. Herein, we used quantitative real-time polymerase chain reaction (qRT-PCR) to identify TF genes affected during SE induced by in vitro culture in Arabidopsis thaliana. Expression profiles of 1,880 TFs were evaluated in the highly embryogenic Col-0 accession and the non-embryogenic tanmei/emb2757 mutant. Our study revealed 729 TFs whose expression changes during the 10-days incubation period of SE; 141 TFs displayed distinct differences in expression patterns in embryogenic versus non-embryogenic cultures. The embryo-induction stage of SE occurring during the first 5 days of culture was associated with a robust and dramatic change of the TF transcriptome characterized by the drastic up-regulation of the expression of a great majority (over 80%) of the TFs active during embryogenic culture. In contrast to SE induction, the advanced stage of embryo formation showed attenuation and stabilization of transcript levels of many TFs. In total, 519 of the SE-modulated TFs were functionally annotated and transcripts related with plant development, phytohormones and stress responses were found to be most abundant. The involvement of selected TFs in SE was verified using T-DNA insertion lines and a significantly reduced embryogenic response was found for the majority of them. This study provides comprehensive data focused on the expression of TF genes during SE and suggests directions for further research on functional genomics of SE.
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