Abstract
Hox proteins play fundamental roles in controlling morphogenetic diversity along the anterior–posterior body axis of animals by regulating distinct sets of target genes. Within their rather broad expression domains, individual Hox proteins control cell diversification and pattern formation and consequently target gene expression in a highly localized manner, sometimes even only in a single cell. To achieve this high-regulatory specificity, it has been postulated that Hox proteins co-operate with other transcription factors to activate or repress their target genes in a highly context-specific manner in vivo. However, only a few of these factors have been identified. Here, we analyze the regulation of the cell death gene reaper (rpr) by the Hox protein Deformed (Dfd) and suggest that local activation of rpr expression in the anterior part of the maxillary segment is achieved through a combinatorial interaction of Dfd with at least eight functionally diverse transcriptional regulators on a minimal enhancer. It follows that context-dependent combinations of Hox proteins and other transcription factors on small, modular Hox response elements (HREs) could be responsible for the proper spatio-temporal expression of Hox targets. Thus, a large number of transcription factors are likely to be directly involved in Hox target gene regulation in vivo.
Highlights
Distinct morphological structures exist along the anteriorposterior (A/P) axes of animals, and the Hox genes represent the major regulators for patterning of this body axis in organisms as diverse as fruit flies, fish and humans [1,2,3]
In line with the very diverse and many-fold effects of Hox proteins on morphogenesis, Hox transcription factors are known to regulate a large number of Hox downstream genes [7,8], including genes that themselves have broad effects on morphology, as well as genes involved in terminal differentiation [reviewed in 3]
By analysing the mechanism underlying the regulation of the Hox target gene reaper, we identified a set of eight transcription factors to be important for the precise spatio-temporal regulation of this gene
Summary
Distinct morphological structures exist along the anteriorposterior (A/P) axes of animals, and the Hox genes represent the major regulators for patterning of this body axis in organisms as diverse as fruit flies, fish and humans [1,2,3]. Some downstream genes can be activated and repressed by the same Hox protein depending on the tissue or developmental stage This context dependency allows a single Hox protein to affect distinct sets of target genes in the same cells during the course of development [8,11,17]. While more and more of these complex regulatory interactions are being described, the molecular mechanisms underlying the spatio-temporal precision of Hox target gene regulation is only poorly understood. This is in large part due to our limited knowledge of the design and function of
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