Roles for Intrinsic Disorder and Fuzziness in Generating Context-specific Function in Ultrabithorax, a Hox Transcription Factor

2012 ◽  
pp. 86-105 ◽  
Author(s):  
Sarah E. Bondos ◽  
Hao-Ching Hsiao
Keyword(s):  
Transcription Factor ◽  
Intrinsic Disorder ◽  
Specific Function ◽  
Context Specific

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo

Development ◽  
2015 ◽  
Vol 142 (11) ◽  
pp. 2069-2079 ◽  
Author(s):  
N. Fossat ◽  
C. K. Ip ◽  
V. J. Jones ◽  
J. B. Studdert ◽  
P.-L. Khoo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mouse Embryo ◽  
Specific Function ◽  
Head Formation ◽  
Context Specific

scholarly journals Context-Specific Transcription Factor Functions Regulate Epigenomic and Transcriptional Dynamics during Cardiac Reprogramming

2019 ◽  
Vol 25 (1) ◽  
pp. 87-102.e9 ◽  
Author(s):  
Nicole R. Stone ◽  
Casey A. Gifford ◽  
Reuben Thomas ◽  
Karishma J.B. Pratt ◽  
Kaitlen Samse-Knapp ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Specific Transcription Factor ◽  
Transcriptional Dynamics ◽  
Context Specific

scholarly journals Evolutionary conservation of the intrinsic disorder-based Radical-Induced Cell Death1 hub interactome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lise Friis Christensen ◽  
Lasse Staby ◽  
Katrine Bugge ◽  
Charlotte O’Shea ◽  
Birthe B. Kragelund ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stress Responses ◽  
Plant Stress ◽  
Three Dimensional ◽  
Intrinsic Disorder ◽  
Dimensional Structure ◽  
Linear Motif ◽  
Intrinsically Disordered ◽  
Helix Formation ◽  
Α Helix

AbstractRadical-Induced Cell Death1 (RCD1) functions as a cellular hub interacting with intrinsically disordered transcription factor regions, which lack a well-defined three-dimensional structure, to regulate plant stress. Here, we address the molecular evolution of the RCD1-interactome. Using bioinformatics, its history was traced back more than 480 million years to the emergence of land plants with the RCD1-binding short linear motif (SLiM) identified from mosses to flowering plants. SLiM variants were biophysically verified to be functional and to depend on the same RCD1 residues as the DREB2A transcription factor. Based on this, numerous additional members may be assigned to the RCD1-interactome. Conservation was further strengthened by similar intrinsic disorder profiles of the transcription factor homologs. The unique structural plasticity of the RCD1-interactome, with RCD1-binding induced α-helix formation in DREB2A, but not detectable in ANAC046 or ANAC013, is apparently conserved. Thermodynamic analysis also indicated conservation with interchangeability between Arabidopsis and soybean RCD1 and DREB2A, although with fine-tuned co-evolved binding interfaces. Interruption of conservation was observed, as moss DREB2 lacked the SLiM, likely reflecting differences in plant stress responses. This whole-interactome study uncovers principles of the evolution of SLiM:hub-interactions, such as conservation of α-helix propensities, which may be paradigmatic for disorder-based interactomes in eukaryotes.

HSF Transcription Factor Family, Heat Shock Response, and Protein Intrinsic Disorder

2012 ◽  
Vol 13 (1) ◽  
pp. 86-103 ◽  
Author(s):  
Sandy D. Westerheide ◽  
Rachel Raynes ◽  
Chase Powell ◽  
Bin Xue ◽  
Vladimir N. Uversky
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Intrinsic Disorder ◽  
Transcription Factor Family ◽  
Shock Response ◽  
Protein Intrinsic Disorder

scholarly journals Context Specific Transcription Factor Prediction

2007 ◽  
Vol 35 (6) ◽  
pp. 1053-1067 ◽  
Author(s):  
Eric Yang ◽  
David Simcha ◽  
Richard R. Almon ◽  
Debra C. Dubois ◽  
William J. Jusko ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Specific Transcription Factor ◽  
Context Specific

scholarly journals Tuned polymerization of the transcription factor Yan limits off-DNA sequestration to confer context-specific repression

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
C Matthew Hope ◽  
Jemma L Webber ◽  
Sherzod A Tokamov ◽  
Ilaria Rebay
Keyword(s):  
Transcription Factor ◽  
Protein Interactions ◽  
Genetic Interaction ◽  
Protein Protein Interactions ◽  
Regulate Gene Expression ◽  
Sam Domain ◽  
Ets Domain ◽  
Context Specific ◽  
Regulatory Decisions ◽  
Type Specification

During development, transcriptional complexes at enhancers regulate gene expression in complex spatiotemporal patterns. To achieve robust expression without spurious activation, the affinity and specificity of transcription factor–DNA interactions must be precisely balanced. Protein–protein interactions among transcription factors are also critical, yet how their affinities impact enhancer output is not understood. The Drosophila transcription factor Yan provides a well-suited model to address this, as its function depends on the coordinated activities of two independent and essential domains: the DNA-binding ETS domain and the self-associating SAM domain. To explore how protein–protein affinity influences Yan function, we engineered mutants that increase SAM affinity over four orders of magnitude. This produced a dramatic subcellular redistribution of Yan into punctate structures, reduced repressive output and compromised survival. Cell-type specification and genetic interaction defects suggest distinct requirements for polymerization in different regulatory decisions. We conclude that tuned protein–protein interactions enable the dynamic spectrum of complexes that are required for proper regulation.

scholarly journals Accurate differential analysis of transcription factor activity from gene expression

2018 ◽  
Author(s):  
Viren Amin ◽  
Murat Can Cobanoglu
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Expression Data ◽  
Differential Analysis ◽  
Gene Regulatory ◽  
Context Specific ◽  
Tf Gene ◽  
Perturbation Estimation

AbstractWe present EPEE (Effector and Perturbation Estimation Engine), a method for differential analysis of transcription factor (TF) activity from gene expression data. EPEE addresses two principal challenges in the field, namely incorporating context-specific TF-gene regulatory networks, and accounting for the fact that TF activity inference is intrinsically coupled for all TFs that share targets. Our validations in well-studied immune and cancer contexts show that addressing the overlap challenge and using state-of-the-art regulatory networks enable EPEE to consistently produce accurate results. (Accessible at: https://github.com/Cobanoglu-Lab/EPEE)

scholarly journals Drugging Fuzzy Complexes in Transcription

2021 ◽  
Vol 8 ◽  
Author(s):  
Bonnie G. Su ◽  
Matthew J. Henley
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Drug Discovery ◽  
Drug Design ◽  
Drug Targets ◽  
Chemical Biology ◽  
Intrinsic Disorder ◽  
High Degree ◽  
Screening Approaches

Transcription factors (TFs) are one of the most promising but underutilized classes of drug targets. The high degree of intrinsic disorder in both the structure and the interactions (i.e., “fuzziness”) of TFs is one of the most important challenges to be addressed in this context. Here, we discuss the impacts of fuzziness on transcription factor drug discovery, describing how disorder poses fundamental problems to the typical drug design, and screening approaches used for other classes of proteins such as receptors or enzymes. We then speculate on ways modern biophysical and chemical biology approaches could synergize to overcome many of these challenges by directly addressing the challenges imposed by TF disorder and fuzziness.

Sign in / Sign up

Export Citation Format

Share Document