TY - JOUR

T1 - Differential pleiotropy and HOX functional organization

AU - Sivanantharajah, Lovesha

AU - Percival-Smith, Anthony

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Key studies led to the idea that transcription factors are composed of defined modular protein motifs or domains, each with separable, unique function. During evolution, the recombination of these modular domains could give rise to transcription factors with new properties, as has been shown using recombinant molecules. This archetypic, modular view of transcription factor organization is based on the analyses of a few transcription factors such as GAL4, which may represent extreme exemplars rather than an archetype or the norm. Recent work with a set of Homeotic selector (HOX) proteins has revealed differential pleiotropy: the observation that highly-conserved HOX protein motifs and domains make small, additive, tissue specific contributions to HOX activity. Many of these differentially pleiotropic HOX motifs may represent plastic sequence elements called short linear motifs (SLiMs). The coupling of differential pleiotropy with SLiMs, suggests that protein sequence changes in HOX transcription factors may have had a greater impact on morphological diversity during evolution than previously believed. Furthermore, differential pleiotropy may be the genetic consequence of an ensemble nature of HOX transcription factor allostery, where HOX proteins exist as an ensemble of states with the capacity to integrate an extensive array of developmental information. Given a new structural model for HOX functional domain organization, the properties of the archetypic TF may require reassessment.

AB - Key studies led to the idea that transcription factors are composed of defined modular protein motifs or domains, each with separable, unique function. During evolution, the recombination of these modular domains could give rise to transcription factors with new properties, as has been shown using recombinant molecules. This archetypic, modular view of transcription factor organization is based on the analyses of a few transcription factors such as GAL4, which may represent extreme exemplars rather than an archetype or the norm. Recent work with a set of Homeotic selector (HOX) proteins has revealed differential pleiotropy: the observation that highly-conserved HOX protein motifs and domains make small, additive, tissue specific contributions to HOX activity. Many of these differentially pleiotropic HOX motifs may represent plastic sequence elements called short linear motifs (SLiMs). The coupling of differential pleiotropy with SLiMs, suggests that protein sequence changes in HOX transcription factors may have had a greater impact on morphological diversity during evolution than previously believed. Furthermore, differential pleiotropy may be the genetic consequence of an ensemble nature of HOX transcription factor allostery, where HOX proteins exist as an ensemble of states with the capacity to integrate an extensive array of developmental information. Given a new structural model for HOX functional domain organization, the properties of the archetypic TF may require reassessment.

KW - Allosteric Site

KW - Alternative Splicing

KW - Amino Acid Motifs

KW - Amino Acid Sequence

KW - Animals

KW - Drosophila Proteins/metabolism

KW - Drosophila melanogaster

KW - Gene Expression Regulation, Developmental

KW - Genes, Homeobox

KW - Homeodomain Proteins/metabolism

KW - Humans

KW - Molecular Sequence Data

KW - Peptides/chemistry

KW - Protein Structure, Tertiary

KW - Transcription Factors/metabolism

U2 - 10.1016/j.ydbio.2014.11.001

DO - 10.1016/j.ydbio.2014.11.001

M3 - Review article

C2 - 25448696

VL - 398

SP - 1

EP - 10

JO - Development Biology

JF - Development Biology

SN - 0012-1606

IS - 1

ER -