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

Merabet, Samir; Hudry, Bruno

doi:10.1002/bies.201200146

Cited by 10 publications

(12 citation statements)

References 30 publications

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“…Paralog-specific repression is mediated by a region in the Hoxc9 N-terminus that has no appreciable impact on DNA-binding. Such specific regulatory output might be mediated by the direct recruitment of specific co-regulator(s) or by forming a structurally distinct complex with the TALE cofactors that recruits specific co-regulators (see below and [25]).…”

Section: Flavors Of Hox-tale Target Genesmentioning

confidence: 99%

“…Importantly, the W motif is not the only PBC interaction motif in Hox proteins, and it is even dispensable for some PBC-dependent Hox functions (see [25] for review). The existence of alternative interaction modes between Hox and PBC proteins was definitively established with the identification of novel PBC interaction motifs in several Drosophila Hox proteins [45–47].…”

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

confidence: 99%

“…Further, they are used in a paralog- and/or species-specific manner for recruiting the TALE cofactors. Based on these properties we collectively refer to them as, “specific PBC interaction motifs “ ( SPIMs ) [25]. The use of different SPIMs in place of or in conjunction with the W motif (Figure 1a) could allow Hox proteins to adopt different 3D-conformations with TALE cofactors, thereby increasing the range of binding sites that are recognized.…”

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

confidence: 99%

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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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Section: Flavors Of Hox-tale Target Genesmentioning

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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

2016

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“…All of them converge to support the predominant role of a unique motif of Hox proteins, called hexapeptide (HX), in making strong interactions with the PBC partner ( Figure 1A). However, these results are in contradiction with the observation that this conserved motif is dispensable in several Hox proteins for interaction and function with TALE cofactors in vivo (Merabet and Hudry, 2013). It is tempting to postulate that the distinct regulatory activities of Hox/TALE complexes rely on their interaction via different protein motifs.…”

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confidence: 56%

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

Merabet

Lohmann

2015

Developmental Cell

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“…It has been previously suggested that the arrangement of Hox-PBC-HMP binding sites may contribute to the activity of Hox-regulated CRM independent of paralog specificity [144]. To test this idea, we recently altered the configuration of Hox sites within the DCRE by swapping them with the Exd/Hth/Hox site found within the RhoA CRM [70].…”

Section: Case Study: the Distal-less Conserved Regulatory Elementmentioning

confidence: 99%

Mechanisms of Specificity for Hox Factor Activity

Zandvakili

Gebelein

2016

JDB

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Metazoans encode clusters of paralogous Hox genes that are critical for proper development of the body plan. However, there are a number of unresolved issues regarding how paralogous Hox factors achieve specificity to control distinct cell fates. First, how do Hox paralogs, which have very similar DNA binding preferences in vitro, drive different transcriptional programs in vivo? Second, the number of potential Hox binding sites within the genome is vast compared to the number of sites bound. Hence, what determines where in the genome Hox factors bind? Third, what determines whether a Hox factor will activate or repress a specific target gene? Here, we review the current evidence that is beginning to shed light onto these questions. In particular, we highlight how cooperative interactions with other transcription factors (especially PBC and HMP proteins) and the sequences of cis-regulatory modules provide a basis for the mechanisms of Hox specificity. We conclude by integrating a number of the concepts described throughout the review in a case study of a highly interrogated Drosophila cis-regulatory module named “The Distal-less Conserved Regulatory Element” (DCRE).

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

Cited by 10 publications

References 30 publications

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

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

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

Mechanisms of Specificity for Hox Factor Activity

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