Toward a New Twist in Hox and TALE DNA-Binding Specificity

Merabet, Samir; Lohmann, Ingrid

doi:10.1016/j.devcel.2015.01.030

Cited by 7 publications

(7 citation statements)

References 10 publications

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“…Perhaps, this is a consequence of a secondary loss of an upstream MEIS or PBC domain in MATα2, necessitating changes in the dimer interactions. However, MEIS proteins may also bind on the other side of the Hox protein as in the class 3 interactions shown in Merabet and Lohmann ( 2015 ) (Fig. 5c ).…”

Section: Dna Binding Of Hd Proteinsmentioning

confidence: 90%

“…MEIS/Hth interacts with PBC through the N-terminal subdomain (PBC-A) (Fig. 5c ) and MEIS/Hth can also interact with the Hox proteins (Amin et al 2015 ; Mann and Affolter 1998 ; Mann et al 2009 ; Merabet and Hudry 2013 ; Merabet and Lohmann 2015 ). In such multimeric complexes, DNA specificity would of course be further increased.…”

Section: Dna Binding Of Hd Proteinsmentioning

confidence: 99%

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Homeodomain proteins: an update

2015

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Here, we provide an update of our review on homeobox genes that we wrote together with Walter Gehring in 1994. Since then, comprehensive surveys of homeobox genes have become possible due to genome sequencing projects. Using the 103 Drosophila homeobox genes as example, we present an updated classification. In animals, there are 16 major classes, ANTP, PRD, PRD-LIKE, POU, HNF, CUT (with four subclasses: ONECUT, CUX, SATB, and CMP), LIM, ZF, CERS, PROS, SIX/SO, plus the TALE superclass with the classes IRO, MKX, TGIF, PBC, and MEIS. In plants, there are 11 major classes, i.e., HD-ZIP (with four subclasses: I to IV), WOX, NDX, PHD, PLINC, LD, DDT, SAWADEE, PINTOX, and the two TALE classes KNOX and BEL. Most of these classes encode additional domains apart from the homeodomain. Numerous insights have been obtained in the last two decades into how homeodomain proteins bind to DNA and increase their specificity by interacting with other proteins to regulate cell- and tissue-specific gene expression. Not only protein-DNA base pair contacts are important for proper target selection; recent experiments also reveal that the shape of the DNA plays a role in specificity. Using selected examples, we highlight different mechanisms of homeodomain protein-DNA interaction. The PRD class of homeobox genes was of special interest to Walter Gehring in the last two decades. The PRD class comprises six families in Bilateria, and tinkers with four different motifs, i.e., the PAIRED domain, the Groucho-interacting motif EH1 (aka Octapeptide or TN), the homeodomain, and the OAR motif. Homologs of the co-repressor protein Groucho are also present in plants (TOPLESS), where they have been shown to interact with small amphipathic motives (EAR), and in yeast (TUP1), where we find an EH1-like motif in MATα2.Electronic supplementary materialThe online version of this article (doi:10.1007/s00412-015-0543-8) contains supplementary material, which is available to authorized users.

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Section: Dna Binding Of Hd Proteinsmentioning

confidence: 90%

Section: Dna Binding Of Hd Proteinsmentioning

confidence: 99%

Homeodomain proteins: an update

2015

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“…Finally, the recognition of low affinity binding sites that do not fit this consensus may depend on additional SPIM-mediated conformation modes (Figure 4a), as observed for Ubx-Exd and AbdA-Exd complexes bound to the Dll repressor element [45,46]. According to this view, SPIMs would be particularly important for paralog specific binding to non-consensus binding sites and subsequent gene regulation [50]. Further tests of this idea may come from the structural analysis of additional paralog-specific binding sites such as those in rho [22] or svb [14].…”

Section: Flexibility In Hox-tale Interaction Properties and The Recogmentioning

confidence: 99%

To Be Specific or Not: The Critical Relationship Between Hox And TALE Proteins

2016

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Hox proteins are key regulatory transcription factors that act in different tissues of the embryo to provide specific spatial and temporal coordinates to each cell. These patterning functions often depend on the presence of the TALE-homeodomain class cofactors, which form cooperative DNA-binding complexes with all Hox proteins. How this family of cofactors contributes to the highly diverse and specific functions of Hox proteins in vivo remains an important unsolved question. Here we review the most recent advances in understanding the molecular mechanisms underlying Hox-TALE function. In particular, we discuss the role of DNA shape, DNA- binding affinity and protein-protein interaction flexibility in dictating Hox-TALE specificity. We propose several models to explain how these mechanisms are integrated with each other in the context of the many distinct functions Hox and TALE factors carry out in vivo.

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“…In particular, the interaction with the three-amino acids loop extension (TALE) family of HDcontaining TFs has been extensively studied, which includes the Drosophila Extradenticle (Exd) and the vertebrate Pbx1-4 proteins 20 . These proteins cooperatively bind DNA with Hox TFs thereby increasing their regulatory specificity [20][21][22][23] . Hox-TALE interactions are mostly mediated via a short hexapeptide (HX) motif, which lies upstream of the Hox HD 24 , and alternatively via the UbdA domain, a protein motif found downstream of the HD in the two Hox TFs Ultrabithorax (Ubx) and Abdominal-A (Abd-A) 25,26 .…”

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confidence: 99%

Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity

et al. 2020

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Transcription factors (TFs) control cell fates by precisely orchestrating gene expression. However, how individual TFs promote transcriptional diversity remains unclear. Here, we use the Hox TF Ultrabithorax (Ubx) as a model to explore how a single TF specifies multiple cell types. Using proximity-dependent Biotin IDentification in Drosophila, we identify Ubx interactomes in three embryonic tissues. We find that Ubx interacts with largely non-overlapping sets of proteins with few having tissue-specific RNA expression. Instead most interactors are active in many cell types, controlling gene expression from chromatin regulation to the initiation of translation. Genetic interaction assays in vivo confirm that they act strictly lineage-and process-specific. Thus, functional specificity of Ubx seems to play out at several regulatory levels and to result from the controlled restriction of the interaction potential by the cellular environment. Thereby, it challenges long-standing assumptions such as differential RNA expression as determinant for protein complexes.

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Toward a New Twist in Hox and TALE DNA-Binding Specificity

Cited by 7 publications

References 10 publications

Homeodomain proteins: an update

Homeodomain proteins: an update

To Be Specific or Not: The Critical Relationship Between Hox And TALE Proteins

Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity

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