Differential pleiotropy and HOX functional organization
Research output: Contribution to journal › Review article › peer-review
Electronic versions
DOI
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.
Keywords
- Allosteric Site, Alternative Splicing, Amino Acid Motifs, Amino Acid Sequence, Animals, Drosophila Proteins/metabolism, Drosophila melanogaster, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins/metabolism, Humans, Molecular Sequence Data, Peptides/chemistry, Protein Structure, Tertiary, Transcription Factors/metabolism
Original language | English |
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Pages (from-to) | 1-10 |
Number of pages | 10 |
Journal | Development Biology |
Volume | 398 |
Issue number | 1 |
Early online date | 11 Nov 2014 |
DOIs | |
Publication status | Published - 1 Feb 2015 |
Externally published | Yes |