scholarly journals Dissociation rate compensation mechanism for budding yeast pioneer transcription factors

2018 ◽  
Author(s):  
Benjamin T. Donovan ◽  
Hengye Chen ◽  
Caroline Jipa ◽  
Lu Bai ◽  
Michael G. Poirier
Keyword(s):  
Transcription Factors ◽  
Small Group ◽  
Migration Rate ◽  
Dwell Time ◽  
Budding Yeast ◽  
Dissociation Rate ◽  
Compensation Mechanism ◽  
Naked Dna ◽  
Pioneer Factors ◽  
Dna Trapping

AbstractNucleosomes restrict the occupancy of most transcription factors (TF) by reducing binding and accelerating dissociation, while a small group of TFs have high affinities to nucleosome-embedded sites and facilitate nucleosome displacement. To mechanistically understand this process, we investigated two S. cerevisiae TFs, Reb1 and Cbf1. We show these factors bind their sites within nucleosomes with similar affinities to naked DNA, trapping a partially unwrapped nucleosome without histone eviction. Both the binding and dissociation rates of Reb1 and Cbf1 are significantly slower at the nucleosomal sites relative to DNA, demonstrating that the high affinities are achieved by increasing the dwell time on nucleosomes to compensate for reduced binding. Reb1 also shows slow migration rate in the yeast nuclei. These properties are similar to human pioneer factors (PFs), suggesting the mechanism of nucleosome targeting is conserved from yeast to human.

scholarly journals Dissociation rate compensation mechanism for budding yeast pioneer transcription factors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Benjamin T Donovan ◽  
Hengye Chen ◽  
Caroline Jipa ◽  
Lu Bai ◽  
Michael G Poirier
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factors ◽  
Migration Rate ◽  
Dwell Time ◽  
Dissociation Rate ◽  
Binding Affinities ◽  
Compensation Mechanism ◽  
Naked Dna ◽  
Pioneer Factors ◽  
Dna Trapping

Nucleosomes restrict the occupancy of most transcription factors (TF) by reducing binding and accelerating dissociation, while a small group of TFs have high affinities to nucleosome-embedded sites and facilitate nucleosome displacement. To understand this process mechanistically, we investigated two Saccharomyces cerevisiae TFs, Reb1 and Cbf1. We show that these factors bind to their sites within nucleosomes with similar binding affinities as to naked DNA, trapping a partially unwrapped nucleosome without histone eviction. Both the binding and dissociation rates of Reb1 and Cbf1 are significantly slower at the nucleosomal sites relative to those for naked DNA, demonstrating that the high affinities are achieved by increasing the dwell time on nucleosomes in order to compensate for reduced binding. Reb1 also shows slow migration rate in the yeast nuclei. These properties are similar to those of human pioneer factors (PFs), suggesting that the mechanism of nucleosome targeting is conserved from yeast to humans.

scholarly journals Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast

PLoS Biology ◽  
2009 ◽  
Vol 7 (10) ◽  
pp. e1000221 ◽  
Author(s):  
Stefano Di Talia ◽  
Hongyin Wang ◽  
Jan M. Skotheim ◽  
Adam P. Rosebrock ◽  
Bruce Futcher ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Size ◽  
Budding Yeast ◽  
Size Control ◽  
Cell Size Control

scholarly journals The stress-regulatory transcription factors Msn2 and Msn4 regulate fatty acid oxidation in budding yeast

2017 ◽  
Vol 292 (45) ◽  
pp. 18628-18643 ◽  
Author(s):  
Praveen Kumar Rajvanshi ◽  
Madhuri Arya ◽  
Ram Rajasekharan
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Budding Yeast ◽  
Acid Oxidation

scholarly journals Binding of transcription factors creates hot spots for UV photoproducts in vivo

1992 ◽  
Vol 12 (4) ◽  
pp. 1798-1804
Author(s):  
G P Pfeifer ◽  
R Drouin ◽  
A D Riggs ◽  
G P Holmquist
Keyword(s):  
Transcription Factors ◽  
Hot Spots ◽  
Mammalian Cells ◽  
Phosphoglycerate Kinase ◽  
Promoter Sequence ◽  
Mean Value ◽  
Naked Dna ◽  
Dna Photoproducts ◽  
Uv Photoproducts

Cyclobutane dipyrimidines and less than mean value of 6-4 dipyrimidines are the two major classes of mutagenic DNA photoproducts produced by UV irradiation of cells. We developed a method to map cyclobutane dipyrimidines at the DNA sequence level in mammalian cells. The frequency of this class of photoproducts was determined at every dipyrimidine along the human phosphoglycerate kinase-1 (PGK1) promoter sequence and was compared to the UV-induced frequency distribution of mean value of 6-4 dipyrimidines. After irradiation of living cells containing active or inactive PGK1 genes, enzymatic or chemical cleavage at UV photoproducts, and amplification by ligation-mediated polymerase chain reaction, photofootprints were seen in all regions which bind transcription factors and appear as DNase I footprints. Photoproduct frequency within transcription factor binding sites was suppressed or enhanced relative to inactive genes or naked DNA with enhancements of up to 30-fold. Since photoproducts are mutagenic, this indicates that photoproduct (mutation?) hot spots may be tissue specific in mammals.

scholarly journals Establishment of chromatin accessibility by the conserved transcription factor Grainy head is developmentally regulated

2019 ◽  
Author(s):  
Markus Nevil ◽  
Tyler J. Gibson ◽  
Constantine Bartolutti ◽  
Anusha Iyengar ◽  
Melissa M Harrison
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Chromatin Accessibility ◽  
Mitotic Chromosomes ◽  
Developmentally Regulated ◽  
Regulatory Modules ◽  
Pioneer Factor ◽  
Pioneer Factors ◽  
Coordinate Changes ◽  
Accessible Chromatin

AbstractThe dramatic changes in gene expression required for development necessitate the establishment of cis-regulatory modules defined by regions of accessible chromatin. Pioneer transcription factors have the unique property of binding closed chromatin and facilitating the establishment of these accessible regions. Nonetheless, much of how pioneer transcription factors coordinate changes in chromatin accessibility during development remains unknown. To determine whether pioneer-factor function is intrinsic to the protein or whether pioneering activity is developmentally modulated, we studied the highly conserved, essential transcription factor, Grainy head (Grh). Grh is expressed throughout Drosophila development and functions as a pioneer factor in the larvae. We demonstrated that Grh remains bound to condensed mitotic chromosomes, a property shared with other pioneer factors. By assaying chromatin accessibility in embryos lacking either maternal or zygotic Grh at three stages of development, we discovered that Grh is not required for chromatin accessibility in early embryogenesis, in contrast to its essential functions later in development. Our data reveal that the pioneering activity of Grh is temporally regulated and is likely influenced by additional factors expressed at a given developmental stage.

scholarly journals Fragile Gene WWOX Guides TFAP2A/TFAP2C-Dependent Actions Against Tumor Progression in Grade II Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Damian Kołat ◽  
Żaneta Kałuzińska ◽  
Elżbieta Płuciennik
Keyword(s):  
Bladder Cancer ◽  
Transcription Factors ◽  
Matrix Metalloproteinase ◽  
Tumor Cell ◽  
Cell Viability ◽  
Migration Rate ◽  
Matrix Metalloproteinase 2 ◽  
Biological Processes ◽  
Bladder Carcinogenesis ◽  
Grade Ii

IntroductionThe presence of common fragile sites is associated with no-accidental chromosomal instability which occurs prior to carcinogenesis. The WWOX gene spans the second most active fragile site: FRA16D. Chromosomal breakage at this site is more common in bladder cancer patients who are tobacco smokers which suggests the importance of WWOX gene loss regarding bladder carcinogenesis. Tryptophan domains of WWOX are known to recognize motifs of other proteins such as AP-2α and AP-2γ allowing protein-protein interactions. While the roles of both AP-2 transcription factors are important for bladder carcinogenesis, their nature is different. Based on the literature, AP-2γ appears to be oncogenic, whereas AP-2α mainly exhibits tumor suppressor character. Presumably, the interaction between WWOX and both transcription factors regulates thousands of genes, hence the aim of the present study was to determine WWOX, AP-2α, and AP-2γ function in modulating biological processes of bladder cancer.MethodsRT-112 cell line (grade II bladder cancer) was subjected to two stable lentiviral transductions. Overall, this resulted in six variants to investigate distinct WWOX, AP-2α, or AP-2γ function as well as WWOX in collaboration with a particular transcription factor. Cellular models were examined with immunocytochemical staining and in terms of differences in biological processes using assays investigating cell viability, proliferation, apoptosis, adhesion, clonogenicity, migration, activity of metalloproteinases and 3D culture growth.ResultsWWOX overexpression increased apoptosis but decreased cell viability, migration and large spatial colonies. AP-2α overexpression decreased tumor cell viability, migratory potential, matrix metalloproteinase-2 activity and clonogenicity. AP-2γ overexpression decreased matrix metalloproteinase-2 activity but increased wound healing, adhesion, clonogenicity and spatial colony formation. WWOX and AP-2α overexpression induced apoptosis but decreased cell viability, adhesion, matrix metalloproteinase-2 activity, overall number of cultured colonies and migration rate. WWOX and AP-2γ overexpression decreased tumor cell viability, proliferation potential, adhesion, clonogenicity and the ability to create spatial structures, but also increased apoptosis or migration rate.ConclusionCo-overexpression of WWOX with AP-2α or WWOX with AP-2γ resulted in a net anti-tumor effect. However, considering this research findings and the difference between AP-2α and AP-2γ, we suggest that this similarity is due to a divergent behavior of WWOX.

scholarly journals Bioinformatic analysis of the protein/DNA interface

2013 ◽  
Vol 42 (5) ◽  
pp. 3381-3394 ◽  
Author(s):  
Bohdan Schneider ◽  
Jiří Černý ◽  
Daniel Svozil ◽  
Petr Čech ◽  
Jean-Christophe Gelly ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Probabilistic Approach ◽  
Bioinformatic Analysis ◽  
Minor Groove ◽  
Interaction Patterns ◽  
Interacting Protein ◽  
Dna Minor Groove ◽  
Naked Dna ◽  
Dna Conformations ◽  
Protein Blocks

Abstract To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Prots. Struct. Funct. Genet., 41:271–287)] and dinucleotide conformers [Svozil, Kalina, Omelka and Schneider (2008) (DNA conformations and their sequence preferences. Nucleic Acids Res., 36:3690–3706)], respectively. Assembling the mutually interacting protein blocks and dinucleotide conformers into ‘interaction matrices’ revealed their correlations and conformer preferences at the interface relative to their occurrence outside the interface. The analyzed data demonstrated important differences between complexes of various types of proteins such as transcription factors and nucleases, distinct interaction patterns for the DNA minor groove relative to the major groove and phosphate and importance of water-mediated contacts. Water molecules mediate proportionally the largest number of contacts in the minor groove and form the largest proportion of contacts in complexes of transcription factors. The generally known induction of A-DNA forms by complexation was more accurately attributed to A-like and intermediate A/B conformers rare in naked DNA molecules.

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