Human Transcription Factors Contain a High Fraction of Intrinsically Disordered Regions Essential for Transcriptional Regulation

2006 ◽  
Vol 359 (4) ◽  
pp. 1137-1149 ◽  
Author(s):  
Yoshiaki Minezaki ◽  
Keiichi Homma ◽  
Akira R. Kinjo ◽  
Ken Nishikawa
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
High Fraction ◽  
Disordered Regions

scholarly journals The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2868
Author(s):  
Marta Kolonko-Adamska ◽  
Vladimir N. Uversky ◽  
Beata Greb-Markiewicz
Keyword(s):  
Transcription Factors ◽  
Phase Separation ◽  
Posttranslational Modifications ◽  
Wide Spectrum ◽  
In Silico Analysis ◽  
Missense Mutations ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Disordered Regions

The basic helix–loop–helix/Per-ARNT-SIM (bHLH-PAS) proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, ranging from differentiation and development control by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for regulation of their activity. Our aim was to analyze the potential connection between disordered regions of the bHLH-PAS transcription factors, post-transcriptional modifications and liquid-liquid phase separation, in the context of disease-associated missense mutations. Highly flexible disordered regions, enriched in short motives which are more ordered, are responsible for a wide spectrum of interactions with transcriptional co-regulators. Based on our in silico analysis and taking into account the fact that the functions of transcription factors can be modulated by posttranslational modifications and spontaneous phase separation, we assume that the locations of missense mutations inducing disease states are clearly related to sequences directly undergoing these processes or to sequences responsible for their regulation.

scholarly journals The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development

2020 ◽  
Author(s):  
Beata Greb-Markiewicz ◽  
Marta Kolonko-Adamska
Keyword(s):  
Transcription Factors ◽  
Phase Separation ◽  
Wide Spectrum ◽  
In Silico Analysis ◽  
Activity Regulation ◽  
Missense Mutations ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Disordered Regions

The bHLH-PAS proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, from differentiation and development control, by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for their activity regulation. Our aim was to analyse the potential connection between disordered regions of the bHLH-PAS transcription factors with posttranscriptional modifications and liquid-liquid phase separation in the context of the disease-associated missense mutations. Highly flexible disordered regions, enriched in short more ordered motives, are responsible for wide spectrum of interactions with transcriptional co-regulators. Based on our in silico analysis and taking into account fact that transcription factors functions can be modulated by posttranslational modifications and spontaneous phase separation, we assume that the location of missense mutations inducing disease states, is clearly related to sequences directly undergoing these processes or to sequences responsible for their activity regulation.

scholarly journals Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4

2016 ◽  
Vol 25 (11) ◽  
pp. 2006-2017 ◽  
Author(s):  
Emi Hibino ◽  
Rintaro Inoue ◽  
Masaaki Sugiyama ◽  
Jun Kuwahara ◽  
Katsumi Matsuzaki ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

scholarly journals The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors

2019 ◽  
Vol 20 (21) ◽  
pp. 5306 ◽  
Author(s):  
Aneta Tarczewska ◽  
Beata Greb-Markiewicz
Keyword(s):  
Transcription Factors ◽  
Phase Separation ◽  
Transcription Regulation ◽  
Experimental Studies ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Wide Range ◽  
Bhlh Transcription Factors ◽  
Bhlh Proteins ◽  
Disordered Regions

The bHLH proteins are a family of eukaryotic transcription factors regulating expression of a wide range of genes involved in cell differentiation and development. They contain the Helix-Loop-Helix (HLH) domain, preceded by a stretch of basic residues, which are responsible for dimerization and binding to E-box sequences. In addition to the well-preserved DNA-binding bHLH domain, these proteins may contain various additional domains determining the specificity of performed transcriptional regulation. According to this, the family has been divided into distinct classes. Our aim was to emphasize the significance of existing disordered regions within the bHLH transcription factors for their functionality. Flexible, intrinsically disordered regions containing various motives and specific sequences allow for multiple interactions with transcription co-regulators. Also, based on in silico analysis and previous studies, we hypothesize that the bHLH proteins have a general ability to undergo spontaneous phase separation, forming or participating into liquid condensates which constitute functional centers involved in transcription regulation. We shortly introduce recent findings on the crucial role of the thermodynamically liquid-liquid driven phase separation in transcription regulation by disordered regions of regulatory proteins. We believe that further experimental studies should be performed in this field for better understanding of the mechanism of gene expression regulation (among others regarding oncogenes) by important and linked to many diseases the bHLH transcription factors.

scholarly journals Walking the DNA Methylation Tightrope: The Involvement of Intrinsically Disordered Regions of Transcription Factors

2017 ◽  
Vol 112 (3) ◽  
pp. 207a
Author(s):  
Stephanie M. Bilinovich ◽  
Hai Pan ◽  
Parminder Kaur ◽  
Hong Wang ◽  
David C. Williams
Keyword(s):  
Dna Methylation ◽  
Transcription Factors ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions
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