scholarly journals Mutational processes in cancer preferentially affect binding of particular transcription factors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mo Liu ◽  
Arnoud Boot ◽  
Alvin W. T. Ng ◽  
Raluca Gordân ◽  
Steven G. Rozen

AbstractProtein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial progress in dissecting the patterns of mutations, i.e., the "mutational signatures", generated by different mutational processes. By combining these two layers of information we can investigate whether certain mutational processes tend to preferentially affect binding of particular classes of TFs. Such preferential alterations of binding might predispose to particular oncogenic pathways. We developed and implemented a method, termed "Signature-QBiC", that integrates protein binding microarray data with the signatures of mutational processes, with the aim of predicting which TFs’ binding profiles are preferentially perturbed by particular mutational processes. We used Signature-QBiC to predict the effects of 47 signatures of mutational processes on 582 human TFs. Pathway analysis showed that binding of TFs involved in NOTCH1 signaling is strongly affected by the signatures of several mutational processes, including exposure to ultraviolet radiation. Additionally, toll-like-receptor signaling pathways are also vulnerable to disruption by this exposure. This study provides a novel overview of the effects of mutational processes on TF binding and the potential of these processes to activate oncogenic pathways through mutating TF binding sites.

2020 ◽  
Author(s):  
JOUNG SUG KIM ◽  
SongHwa Chae ◽  
Kyong Mi Jun ◽  
Gang-Seob Lee ◽  
Jong-Seong Jeon ◽  
...  

Abstract The authors have withdrawn this preprint due to author disagreement.


2011 ◽  
Vol 66 (4) ◽  
pp. 700-711 ◽  
Author(s):  
Marta Godoy ◽  
José M. Franco-Zorrilla ◽  
Julián Pérez-Pérez ◽  
Juan C. Oliveros ◽  
Óscar Lorenzo ◽  
...  

2020 ◽  
Author(s):  
JOUNG SUG KIM ◽  
SongHwa Chae ◽  
Kyong Mi Jun ◽  
Gang-Seob Lee ◽  
Jong-Seong Jeon ◽  
...  

Abstract BackgroundTranscription factors (TFs) regulate the expression of genes at the transcriptional level by binding a specific DNA sequence. Thus, predicting the DNA-binding motifs of TFs is one of the most important areas for the functional analysis of TFs in the postgenomic era. Although many methods have been developed for this challenge, there are still many TFs with unknown DNA-binding motifs.FindingsIn this paper, we designed an rice (Oryza sativa)-specific protein binding microarray (RPBM), and its probes are 40 bp long with 20 bp of overlap; there are 49 probes spanning the 1 kb promoter region before the translation start site of each gene. To confirm the efficiency of RPBM technology, we selected two TFs, OsWOX13 and OsSMF1. We identified the ATTGATTG DNA-binding sequence and 635 putative target genes of OsWOX13. OsSMF1 bound to GCTGACTCA and GGATGCC sequences and bound especially strongly to CCACGTCA. A total of 932 putative target genes were identified for OsSMF1.ConclusionsRPBM can be applicable in the analysis of DNA-binding motifs for TFs where binding is evaluated in extended natural promoter regions. The analysis can also be applicable to TFs that have single or multiple binding motifs. The technology might even be expanded for application to TFs that are heterodimers or form higher-order complexes.


1987 ◽  
Vol 7 (12) ◽  
pp. 4560-4563
Author(s):  
B Devaux ◽  
G Albrecht ◽  
C Kedinger

Genomic DNase I footprinting was used to compare specific protein binding to the adenovirus type 5 early, EIa-inducible, EIIa promoter. Identical protection patterns of the promoter region were observed whether EIIa transcription was undetectable or fully induced. These results suggest that EIa-mediated transcriptional induction does not increase binding of limiting transcription factors to the promoter but rather that transactivation results from the proper interactions between factors already bound to their cognate sequences.


2010 ◽  
pp. 1075-1075
Author(s):  
R. Hamish McAllister-Williams ◽  
Daniel Bertrand ◽  
Hans Rollema ◽  
Raymond S. Hurst ◽  
Linda P. Spear ◽  
...  

2017 ◽  
Vol 114 (29) ◽  
pp. E5995-E6004 ◽  
Author(s):  
Yan O. Zubo ◽  
Ivory Clabaugh Blakley ◽  
Maria V. Yamburenko ◽  
Jennifer M. Worthen ◽  
Ian H. Street ◽  
...  

The plant hormone cytokinin affects a diverse array of growth and development processes and responses to the environment. How a signaling molecule mediates such a diverse array of outputs and how these response pathways are integrated with other inputs remain fundamental questions in plant biology. To this end, we characterized the transcriptional network initiated by the type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs) that mediate the cytokinin primary response, making use of chromatin immunoprecipitation sequencing (ChIP-seq), protein-binding microarrays, and transcriptomic approaches. By ectopic overexpression of ARR10, Arabidopsis lines hypersensitive to cytokinin were generated and used to clarify the role of cytokinin in regulation of various physiological responses. ChIP-seq was used to identify the cytokinin-dependent targets for ARR10, thereby defining a crucial link between the cytokinin primary-response pathway and the transcriptional changes that mediate physiological responses to this phytohormone. Binding of ARR10 was induced by cytokinin with binding sites enriched toward the transcriptional start sites for both induced and repressed genes. Three type-B ARR DNA-binding motifs, determined by use of protein-binding microarrays, were enriched at ARR10 binding sites, confirming their physiological relevance. WUSCHEL was identified as a direct target of ARR10, with its cytokinin-enhanced expression resulting in enhanced shooting in tissue culture. Results from our analyses shed light on the physiological role of the type-B ARRs in regulating the cytokinin response, mechanism of type-B ARR activation, and basis by which cytokinin regulates diverse aspects of growth and development as well as responses to biotic and abiotic factors.


2020 ◽  
Vol 21 (18) ◽  
pp. 6951
Author(s):  
Ting Jia ◽  
Yuting Cheng ◽  
Imran Khan ◽  
Xuan Zhao ◽  
Tongyu Gu ◽  
...  

Edible fleshy fruits are important food sources in the human diet. Their yield and nutritional quality have long been considered as breeding targets for improvement. Various developing fleshy fruits with functional chloroplasts are capable of photosynthesis and contribute to fruit photosynthate, leading to the accumulation of metabolites associated with nutritional quality in ripe fruit. Although tomato high-pigment mutants with dark-green fruits have been isolated for more than 100 years, our understanding of the mechanism of chloroplast development in fleshy fruit remain poor. During the past few years, several transcription factors that regulate chloroplast development in fleshy fruit were identified through map-based cloning. In addition, substantial progress has been made in elucidating the mechanisms that how these transcription factors regulate chloroplast development. This review provides a summary and update on this progress, with a framework for further investigations of the multifaceted and hierarchical regulation of chloroplast development in fleshy fruit.


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