Abstract
Extradenticle (Exd) and Homothorax (Hth) function as positive transcriptional cofactors of Hox proteins, helping them to bind specifically their direct targets. The posterior Hox protein Abdominal-B (Abd-B) does not require Exd/Hth to bind DNA; and, during embryogenesis, Abd-B represses hth and exd transcription. Here we show that this repression is necessary for Abd-B function, as maintained Exd/Hth expression results in transformations similar to those observed in loss-of-function Abd-B mutants. We characterize the cis regulatory module directly regulated by Abd-B in the empty spiracles gene and show that the Exd/Hth complex interferes with Abd-B binding to this enhancer. Our results suggest that this novel Exd/Hth function does not require the complex to bind DNA and may be mediated by direct Exd/Hth binding to the Abd-B homeodomain. Thus, in some instances, the main positive cofactor complex for anterior Hox proteins can act as a negative factor for the posterior Hox protein Abd-B. This antagonistic interaction uncovers an alternative way in which MEIS and PBC cofactors can modulate Abd-B like posterior Hox genes during development.
Highlights
In segmented animals the differential anterior-posterior morphology is achieved during development under the control of the Hox genes [1]
The evolution of Hox proteins was fundamental for the acquisition of morphological differences in the antero-posterior axis of animals
Comparison between all extant animals indicates that the difference between posterior (Abd-B like) and anteriorHox genes occurred early in evolution
Summary
In segmented animals the differential anterior-posterior morphology is achieved during development under the control of the Hox genes [1]. Hox genes encode a conserved family of transcription factors organized in clusters in most animals. The development of the unique organs present in a segment is controlled by the Hox protein expressed in that segment through the regulation of specific downstream targets. In Drosophila melanogaster the Abdominal-B (Abd-B) protein (orthologous to Hox9/13 in mammals) induces the formation of the posterior spiracles in the eighth abdominal segment (A8) through the transcriptional activation of empty spiracles (ems), cut (ct) and spalt (sal) among other genes [4,5]. Expression of the Sex combs reduced protein (Scr, orthologous to Hox5) in the labial segment of the head induces the formation of the salivary glands through the activation of fork head, trachealess and huckebein [6]; while expression of Ultrabithorax (Ubx) and Abdominal-A
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