Homeotic control in Drosophila; the scabrous gene is an in vivo target of Ultrabithorax proteins.

Graba, Yacine; Aragnol, Denise; Laurenti, Patrick; Garzino, Véronique; Charmot, Dominique; Berenger, H.; Pradel, Jacques

doi:10.1002/j.1460-2075.1992.tb05416.x

Cited by 70 publications

(21 citation statements)

References 73 publications

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“…Although some progress has been made in the identification of downstream candidates for regulation by homeotic proteins (26,28,29,35,39,64,65,77), only recently have systematic studies on the number and arrangement of binding sites required for this regulation begun. We therefore began our characterization of DNA binding by a Ubx protein with U-A and U-B, the first two naturally occurring binding sites to be biochemically identified (7) (see also Discussion).…”

Section: Resultsmentioning

confidence: 99%

Cooperative binding of an Ultrabithorax homeodomain protein to nearby and distant DNA sites.

Beachy¹,

Varkey²,

Young³

et al. 1993

Mol. Cell. Biol.

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Cooperativity in binding of regulatory proteins to multiple DNA sites can heighten the sensitivity and specificity of the transcriptional response. We report here the cooperative DNA-binding properties of a developmentally active regulatory protein encoded by the Drosophila homeotic gene Ultrabithorax (Ubx). We show that naturally occurring binding sites for the Ubx-encoded protein contain clusters of multiple individual binding site sequences. Such sites can form complexes containing a dozen or more Ubx-encoded protein molecules, with simultaneous cooperative interactions between adjacent and distant DNA sites. The distant mode of interaction involves a DNA looping mechanism; both modes appear to enhance transcriptional activation in a simple yeast assay system. We found that cooperative binding is dependent on sequences outside the homeodomain, and we have identified regions predicted to form coiled coils carboxy terminal to the homeodomains of the Ubx-encoded protein and several other homeotic proteins. On the basis of our findings, we propose a multisite integrative model of homeotic protein action in which functional regulatory elements can be built from a few high-affinity sites, from many lower-affinity sites, or from sites of some intermediate number and affinity. An important corollary of this model is that even small differences in binding of homeotic proteins to individual sites could be summed to yield large overall differences in binding to multiple sites. This model is consistent with reports that homeodomain protein targets contain multiple individual binding site sequences distributed throughout sizable DNA regions. Also consistent is a recent report that sequences carboxy terminal to the Ubx homeodomain can contribute to segmental specificity.

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Section: Resultsmentioning

confidence: 99%

Cooperative binding of an Ultrabithorax homeodomain protein to nearby and distant DNA sites.

Beachy¹,

Varkey²,

Young³

et al. 1993

Mol. Cell. Biol.

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“…Consequently, it is thought that their functions rely on the selective activation (or repression) of downstream gene networks. In recent years, the search for Hox target genes has identified a wide range of downstream factors of diverse biological function Graba et al, 1992;Hueber et al, 2007), including regulatory functions (e.g. signalling molecules or components of signalling pathways, transcription factors) and the so-called realisator genes that are more directly involved in morphogenetic processes.…”

Section: Introductionmentioning

confidence: 99%

Cellular and molecular insights into Hox protein action

et al. 2015

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Hox genes encode homeodomain transcription factors that control morphogenesis and have established functions in development and evolution. Hox proteins have remained enigmatic with regard to the molecular mechanisms that endow them with specific and diverse functions, and to the cellular functions that they control. Here, we review recent examples of Hox-controlled cellular functions that highlight their versatile and highly context-dependent activity. This provides the setting to discuss how Hox proteins control morphogenesis and organogenesis. We then summarise the molecular modalities underlying Hox protein function, in particular in light of current models of transcription factor function. Finally, we discuss how functional divergence between Hox proteins might be achieved to give rise to the many facets of their action.

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“…We present a similar approach, performed on a larger scale, leading to a genome-wide view of direct Engrailed-binding loci in embryos. UV light or formaldehyde crosslinking are currently used to purify protein-DNA complexes, and to isolate specific binding fragments (Graba et al, 1992;Serrano et al, 1995;Serrano et al, 1997;Liang and Biggin, 1998;Cavalli et al, 1999;Toth and Biggin, 2000;Weinmann et al, 2001;Weinmann et al, 2002). However, UV light is believed to be more efficient in fixing proteins that are directly bound to DNA (Toth and Biggin, 2000).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide identification of in vivoDrosophilaEngrailed-binding DNA fragments and related target genes

et al. 2003

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Chromatin immunoprecipitation after UV crosslinking of DNA/protein interactions was used to construct a library enriched in genomic sequences that bind to the Engrailed transcription factor in Drosophila embryos. Sequencing of the clones led to the identification of 203 Engrailed-binding fragments localized in intergenic or intronic regions. Genes lying near these fragments, which are considered as potential Engrailed target genes, are involved in different developmental pathways, such as anteroposterior patterning, muscle development, tracheal pathfinding or axon guidance. We validated this approach by in vitro and in vivo tests performed on a subset of Engrailed potential targets involved in these various pathways. Finally, we present strong evidence showing that an immunoprecipitated genomic DNA fragment corresponds to a promoter region involved in the direct regulation of frizzled2 expression by engrailed in vivo.

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Homeotic control in Drosophila; the scabrous gene is an in vivo target of Ultrabithorax proteins.

Cited by 70 publications

References 73 publications

Cooperative binding of an Ultrabithorax homeodomain protein to nearby and distant DNA sites.

Cooperative binding of an Ultrabithorax homeodomain protein to nearby and distant DNA sites.

Cellular and molecular insights into Hox protein action

Genome-wide identification of in vivoDrosophilaEngrailed-binding DNA fragments and related target genes

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