Specific DNA sequences allosterically enhance protein–protein interaction in a transcription factor through modulation of protein dynamics: implications for specificity of gene regulation

2017 ◽  
Vol 19 (22) ◽  
pp. 14781-14792
Author(s):  
Abhishek Mazumder ◽  
Subrata Batabyal ◽  
Manas Mondal ◽  
Tanumoy Mondol ◽  
Susobhan Choudhury ◽  
...  

Most genes are regulated by multiple transcription factors, often assembling into multi-protein complexes in the gene regulatory region.

2018 ◽  
Vol 115 (15) ◽  
pp. E3481-E3490 ◽  
Author(s):  
Joshua L. Payne ◽  
Fahad Khalid ◽  
Andreas Wagner

Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein–RNA interactions and transcription factor–DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.


2017 ◽  
Author(s):  
Allie M. Graham ◽  
Jason S. Presnell

ABSTRACTTranscription factors are characterized by their domain architecture, including DNA binding and protein-protein interaction domain combinations, which regulate their binding specificity, as well as their ability to effect a change on gene expression of their downstream targets. Transcription factors are central to organismal development, thus they potentially are instrumental in producing phenotypic diversity. Transcription factor abundance was estimated via 49 major DNA binding domain families, as well as 34 protein-protein interaction domain families, in 48 bird genomes, which were then compared with 6 available reptile genomes, in an effort to assess the degree to which these domains are potentially connected to increased phenotypic diversity in the avian lineage. We hypothesized that there would be increased abundance in multiple transcription factor domain families, as well as domains associated with protein-protein interactions, that would correlate with the increased phenotypic diversity found in birds; instead, this data shows a general loss/contraction of major domain families, with the largest losses in domain families associated with multiple developmental (feather, body-plan, immune) and metabolic processes. Ultimately, the results of this analyses represent a general characterization of domain family composition in birds, thus the specific domain composition of TF families should be probed further, especially those with the largest reductions seen in this study.


2021 ◽  
Author(s):  
Kaho Suzuki ◽  
Yousuke Takaoka ◽  
Minoru Ueda

Correction for ‘Rational design of a stapled JAZ9 peptide inhibiting protein–protein interaction of a plant transcription factor’ by Kaho Suzuki et al., RSC Chem. Biol., 2021, DOI: 10.1039/d0cb00204f.


2021 ◽  
Author(s):  
Kaho Suzuki ◽  
Yousuke Takaoka ◽  
Minoru Ueda

A rationally designed stapled JAZ peptide selectively inhibited MYCs, master-regulators of the jasmonate signaling in Arabidopsis thaliana. It is proposed as a novel chemical tool for the analysis of MYC related jasmonate signaling.


2004 ◽  
Vol 20 (1) ◽  
pp. 143-151 ◽  
Author(s):  
James Paris ◽  
Carl Virtanen ◽  
Zhibin Lu ◽  
Mark Takahashi

Although a great deal has been elucidated concerning the mechanisms regulating muscle differentiation, little is known about transcription factor-specific gene regulation. Our understanding of the genetic mechanisms regulating cell differentiation is quite limited. Much of what has been defined centers on regulatory signaling cascades and transcription factors. Surprisingly few studies have investigated the association of genes with specific transcription factors. To address these issues, we have utilized a method coupling chromatin immunoprecipitation and CpG microarrays to characterize the genes associated with MEF2 in differentiating C2C12 cells. Results demonstrated a defined binding pattern over the course of differentiation. Filtered data demonstrated 9 clones to be elevated at 0 h, 792 at 6 h, 163 by 1 day, and 316 at 3 days. Using unbiased selection parameters, we selected a subset of 291 prospective candidates. Clones were sequenced and filtered for removal of redundancy between clones and for the presence of repetitive elements. We were able to place 50 of these on the mouse genome, and 20 were found to be located near well-annotated genes. From this list, previously undefined associations with MEF2 were discovered. Many of these genes represent proteins involved in neurogenesis, neuromuscular junctions, signaling and metabolism. The remaining clones include many full-length cDNA and represent novel gene targets. The results of this study provides for the first time, a unique look at gene regulation at the level of transcription factor binding in differentiating muscle.


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