Low affinity binding site clusters confer HOX specificity and regulatory robustness
In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) i...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v160_n1-2_p191_Crocker http://hdl.handle.net/20.500.12110/paper_00928674_v160_n1-2_p191_Crocker |
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paper:paper_00928674_v160_n1-2_p191_Crocker2023-06-08T15:08:26Z Low affinity binding site clusters confer HOX specificity and regulatory robustness DNA fragment Hox protein DNA binding protein Drosophila protein extradenticle protein, Drosophila homeodomain protein ovo protein, Drosophila protein binding transcription factor Ubx protein, Drosophila animal cell Article binding affinity binding site chromatin immunoprecipitation controlled study DNA sequence Drosophila melanogaster Drosophila virilis embryo embryo cell enhancer region gel mobility shift assay genetic conservation genetic regulation genetic variability insect cell natural selection nonhuman priority journal reporter gene trichome wild type animal animal embryo enhancer region gene expression regulation genetics metabolism molecular genetics nucleotide sequence sequence alignment Animalia Animals Base Sequence DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Embryo, Nonmammalian Enhancer Elements, Genetic Gene Expression Regulation Homeodomain Proteins Molecular Sequence Data Protein Binding Sequence Alignment Transcription Factors In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bound specifically to clusters of very low affinity sites in enhancers of the shavenbaby gene of Drosophila. These low affinity sites conferred specificity for Ubx binding in vivo, but multiple clustered sites were required for robust expression when embryos developed in variable environments. Although most individual Ubx binding sites are not evolutionarily conserved, the overall enhancer architecture - clusters of low affinity binding sites - is maintained and required for enhancer function. Natural selection therefore works at the level of the enhancer, requiring a particular density of low affinity Ubx sites to confer both specific and robust expression. © 2015 Elsevier Inc. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v160_n1-2_p191_Crocker http://hdl.handle.net/20.500.12110/paper_00928674_v160_n1-2_p191_Crocker |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
DNA fragment Hox protein DNA binding protein Drosophila protein extradenticle protein, Drosophila homeodomain protein ovo protein, Drosophila protein binding transcription factor Ubx protein, Drosophila animal cell Article binding affinity binding site chromatin immunoprecipitation controlled study DNA sequence Drosophila melanogaster Drosophila virilis embryo embryo cell enhancer region gel mobility shift assay genetic conservation genetic regulation genetic variability insect cell natural selection nonhuman priority journal reporter gene trichome wild type animal animal embryo enhancer region gene expression regulation genetics metabolism molecular genetics nucleotide sequence sequence alignment Animalia Animals Base Sequence DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Embryo, Nonmammalian Enhancer Elements, Genetic Gene Expression Regulation Homeodomain Proteins Molecular Sequence Data Protein Binding Sequence Alignment Transcription Factors |
| spellingShingle |
DNA fragment Hox protein DNA binding protein Drosophila protein extradenticle protein, Drosophila homeodomain protein ovo protein, Drosophila protein binding transcription factor Ubx protein, Drosophila animal cell Article binding affinity binding site chromatin immunoprecipitation controlled study DNA sequence Drosophila melanogaster Drosophila virilis embryo embryo cell enhancer region gel mobility shift assay genetic conservation genetic regulation genetic variability insect cell natural selection nonhuman priority journal reporter gene trichome wild type animal animal embryo enhancer region gene expression regulation genetics metabolism molecular genetics nucleotide sequence sequence alignment Animalia Animals Base Sequence DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Embryo, Nonmammalian Enhancer Elements, Genetic Gene Expression Regulation Homeodomain Proteins Molecular Sequence Data Protein Binding Sequence Alignment Transcription Factors Low affinity binding site clusters confer HOX specificity and regulatory robustness |
| topic_facet |
DNA fragment Hox protein DNA binding protein Drosophila protein extradenticle protein, Drosophila homeodomain protein ovo protein, Drosophila protein binding transcription factor Ubx protein, Drosophila animal cell Article binding affinity binding site chromatin immunoprecipitation controlled study DNA sequence Drosophila melanogaster Drosophila virilis embryo embryo cell enhancer region gel mobility shift assay genetic conservation genetic regulation genetic variability insect cell natural selection nonhuman priority journal reporter gene trichome wild type animal animal embryo enhancer region gene expression regulation genetics metabolism molecular genetics nucleotide sequence sequence alignment Animalia Animals Base Sequence DNA-Binding Proteins Drosophila melanogaster Drosophila Proteins Embryo, Nonmammalian Enhancer Elements, Genetic Gene Expression Regulation Homeodomain Proteins Molecular Sequence Data Protein Binding Sequence Alignment Transcription Factors |
| description |
In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bound specifically to clusters of very low affinity sites in enhancers of the shavenbaby gene of Drosophila. These low affinity sites conferred specificity for Ubx binding in vivo, but multiple clustered sites were required for robust expression when embryos developed in variable environments. Although most individual Ubx binding sites are not evolutionarily conserved, the overall enhancer architecture - clusters of low affinity binding sites - is maintained and required for enhancer function. Natural selection therefore works at the level of the enhancer, requiring a particular density of low affinity Ubx sites to confer both specific and robust expression. © 2015 Elsevier Inc. |
| title |
Low affinity binding site clusters confer HOX specificity and regulatory robustness |
| title_short |
Low affinity binding site clusters confer HOX specificity and regulatory robustness |
| title_full |
Low affinity binding site clusters confer HOX specificity and regulatory robustness |
| title_fullStr |
Low affinity binding site clusters confer HOX specificity and regulatory robustness |
| title_full_unstemmed |
Low affinity binding site clusters confer HOX specificity and regulatory robustness |
| title_sort |
low affinity binding site clusters confer hox specificity and regulatory robustness |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v160_n1-2_p191_Crocker http://hdl.handle.net/20.500.12110/paper_00928674_v160_n1-2_p191_Crocker |
| _version_ |
1768542405656576000 |