A unique Extradenticle recruitment mode in the
            <i>Drosophila</i>
            Hox protein Ultrabithorax

Merabet, Samir; Saadaoui, Mehdi; Sambrani, Nagraj; Hudry, Bruno; Pradel, Jacques; Affolter, Markus; Graba, Yacine

doi:10.1073/pnas.0705832104

Cited by 77 publications

(107 citation statements)

References 35 publications

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“…Because of its conservation in most Hox proteins, the HX has long been considered as a generic and obligatory protein interface for Hox/PBC complex formation. This assumption has recently been challenged by the discovery that other Hox protein motifs could also convey PBCrecruiting activities [21,22]. It was further observed that the formation of vertebrate and invertebrate Hox/PBC complexes could occur in the absence of the HX in vitro and in vivo [22].…”

Section: Introductionmentioning

confidence: 99%

“…One example of semi-instructive binding sites is found in the enhancer of the Distalless (Dll) target gene [29], which can be repressed by different Hox proteins associated through at least three different interaction modes with the PBC cofactor. Other enhancers, such as those of the teashirt (tsh) target gene, also fulfil the definition of semiinstructive binding sites [21].…”

Section: Introductionmentioning

confidence: 99%

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Hox transcriptional specificity despite a single class of cofactors: Are flexible interaction modes the key?

Merabet

Hudry

2012

BioEssays

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Editor's suggested further reading in BioEssays ftz Evolution: Findings, hypotheses and speculations (response to DOI 10.1002/bies.201100019) AbstractOn the border of the homeotic function: Re‐evaluating the controversial role of cofactor‐recruiting motifs AbstractControl of DNA replication: A new facet of Hox proteins? AbstractClassification of sequence signatures: a guide to Hox protein function Abstract

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hox transcriptional specificity despite a single class of cofactors: Are flexible interaction modes the key?

Merabet

Hudry

2012

BioEssays

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“…Mutations of either the HX or UbdA motifs were introduced in Ubx sequences. Although Dm-Ubx (more specifically the Dm-UbxIa isoform, see below) requires the UbdA motif to assemble a Ubx/Exd/Hth complex in vitro (18), Exd interaction by Cs-Ubx, Af-Ubx (22), and Stm-Ubx (23) implicates the HX motif instead (Fig. 1B).…”

Section: Arthropod Ubx Proteins Display Distinct Exd Interaction Modementioning

confidence: 99%

“…To investigate whether these sequence divergences could affect the mode of Hox-Exd association, we performed in vitro band shift experiments, in which trimeric Ubx/Exd/Homothorax (Hth) complex formation on Dll target sequences relies on Ubx-Exd interaction (18,21). Mutations of either the HX or UbdA motifs were introduced in Ubx sequences.…”

Section: Arthropod Ubx Proteins Display Distinct Exd Interaction Modementioning

confidence: 99%

“…This retention is illustrated in vertebrates by the dominant phenotypes resulting from HX mutation of the mouse HoxB-8 protein, which are difficult to reconcile with a lack of Pbx protein interaction (17), and in Drosophila by the retained capacity of HX-mutated AbdominalA (AbdA) and Ultrabithorax (Ubx) proteins to repress the limb-promoting target gene Distalless (Dll) (11,18). In Ubx, a short motif located downstream of the HD conveys Exd interaction potential (18). This motif, UbdA, 8 aa long, is shared exclusively by the central paralog proteins Ubx and AbdA and is found only in protostomes (19,20).…”

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Selection of distinct Hox–Extradenticle interaction modes fine-tunes Hox protein activity

Saadaoui

Merabet

Litim-Mecheri

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Hox genes encode transcription factors widely used for diversifying animal body plans in development and evolution. To achieve functional specificity, Hox proteins associate with PBC class proteins, Pre-B cell leukemia homeobox (Pbx) in vertebrates, and Extradenticle (Exd) in Drosophila, and were thought to use a unique hexapeptide-dependent generic mode of interaction. Recent findings, however, revealed the existence of an alternative, UbdA-dependent paralog-specific interaction mode providing diversity in Hox-PBC interactions. In this study, we investigated the basis for the selection of one of these two Hox-PBC interaction modes. Using naturally occurring variations and mutations in the Drosophila Ultrabithorax protein, we found that the linker region, a short domain separating the hexapeptide from the homeodomain, promotes an interaction mediated by the UbdA domain in a context-dependent manner. While using a UbdA-dependent interaction for the repression of the limb-promoting gene Distalless, interaction with Exd during segment-identity specification still relies on the hexapeptide motif. We further show that distinctly assembled Hox-PBC complexes display subtle but distinct repressive activities. These findings identify Hox-PBC interaction as a template for subtle regulation of Hox protein activity that may have played a major role in the diversification of Hox protein function in development and evolution.transcriptional regulation | AbdominalA | Hox protein specificity and diversity

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Classification of sequence signatures: a guide to Hox protein function

et al. 2009

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Hox proteins are part of the conserved superfamily of homeodomain-containing transcription factors and play fundamental roles in shaping animal body plans in development and evolution. However, molecular mechanisms underlying their diverse and specific biological functions remain largely enigmatic. Here, we have analyzed Hox sequences from the main evolutionary branches of the Bilateria group. We have found that four classes of Hox protein signatures exist, which together provide sufficient support to explain how different Hox proteins differ in their control and function. The homeodomain and its surrounding sequences accumulate nearly all signatures, constituting an extended module where most of the information distinguishing Hox proteins is concentrated. Only a small fraction of these signatures has been investigated at the functional level, but these show that approaches relying on Hox protein alterations still have a large potential for deciphering molecular mechanisms of Hox differential control.

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A unique Extradenticle recruitment mode in the Drosophila Hox protein Ultrabithorax

Cited by 77 publications

References 35 publications

Hox transcriptional specificity despite a single class of cofactors: Are flexible interaction modes the key?

Hox transcriptional specificity despite a single class of cofactors: Are flexible interaction modes the key?

Selection of distinct Hox–Extradenticle interaction modes fine-tunes Hox protein activity

Classification of sequence signatures: a guide to Hox protein function

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