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Antagonism versus cooperativity with TALE cofactors at the base of the functional diversification of hox protein function

AuthorsRivas, María Luisa ; Espinosa-Vázquez, José Manuel; Sambrani, Nagraj; Greig, Stephen; Merabet, Samir; Graba, Yacine; Castelli-Gair Hombría, James
Issue Date2013
PublisherPublic Library of Science
CitationPLoS Genetics 9(2): e1003252 (2013)
AbstractExtradenticle (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.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pgen.1003252
Appears in Collections:(CABD) Artículos
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