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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Drosophila Proteins* / genetics
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Drosophila Proteins* / metabolism
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Drosophila melanogaster* / genetics
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Drosophila melanogaster* / growth & development
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Embryonic Development / genetics*
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Gene Expression Regulation, Developmental
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Homeodomain Proteins* / genetics
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Homeodomain Proteins* / metabolism
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Regulatory Sequences, Nucleic Acid
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Transcription Factors* / genetics
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Transcription Factors* / metabolism
Substances
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Abd-B proteins, Drosophila
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DNA-Binding Proteins
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Drosophila Proteins
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Homeodomain Proteins
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Transcription Factors
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exd protein, Drosophila
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hth protein, Drosophila
Grants and funding
This work was supported by the Programa Consolider, MICINN, European Regional Development Fund (FEDER), and Junta de Andalucía to JC-GH and by an EMBO short-term fellowship to MLR. YG was supported by the CNRS, Université de la Méditerranée, and grants from CEFIPRA, ANR, FRM, and ARC, and by a fellowship from MRT CEFIPRA to NS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.