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PMID: 15795372 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Quantitative analysis of binding motifs mediating diverse spatial readouts of the Dorsal gradient in the Drosophila embryo.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 14 ·2005-04-05 ·Pages 4966-71

Papatsenko D, Levine M

Abstract

Dorsal is a sequence-specific transcription factor that is distributed in a broad nuclear gradient across the dorsal-ventral (DV) axis of the early Drosophila embryo. It initiates gastrulation by regulating at least 30-50 target genes in a concentration-dependent fashion. Previous studies identified 18 enhancers that are directly regulated by different concentrations of Dorsal. Here, we employ computational methods to determine the basis for these distinct transcriptional outputs. Orthologous enhancers were identified in a variety of divergent Drosophila species, and their comparison revealed several conserved sequence features responsible for DV patterning. In particular, the quality of Dorsal and Twist recognition sequences correlates with the DV coordinates of gene expression relative to the Dorsal gradient. These findings are entirely consistent with a gradient threshold model for DV patterning, whereby the quality of individual Dorsal binding sites determines in vivo occupancy of target enhancers by the Dorsal gradient. Linked Dorsal and Twist binding sites constitute a conserved composite element in certain "type 2" Dorsal target enhancers, which direct gene expression in ventral regions of the neurogenic ectoderm in response to intermediate levels of the Dorsal gradient. Similar motif arrangements were identified in orthologous loci in the distant mosquito genome, Anopheles gambiae. We discuss how Dorsal and Twist work either additively or synergistically to activate different target enhancers.

MeSH Terms
Animals Base Sequence Binding Sites/genetics Body Patterning/genetics Conserved Sequence DNA/genetics,metabolism Drosophila Proteins/genetics,metabolism Drosophila melanogaster/embryology,genetics,metabolism Enhancer Elements, Genetic Gene Expression Regulation, Developmental Genes, Insect Models, Genetic Molecular Sequence Data Nuclear Proteins/genetics,metabolism Phosphoproteins/genetics,metabolism Phylogeny Sequence Homology, Nucleic Acid Transcription Factors/genetics,metabolism Twist-Related Protein 1
Chemicals
Drosophila Proteins Nuclear Proteins Phosphoproteins Transcription Factors Twi protein, Drosophila Twist-Related Protein 1 dl protein, Drosophila DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Papatsenko Dmitri
Department of Molecular and Cell Biology, Division of Genetics, Genomics, and Development, Center for Integrative Genomics, University of California, 16 Barker Hall No. 3204, Berkeley, CA 94720-3204, USA. dxp@berkely.edu
Levine Michael
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0409414102
Email
dxp@berkely.edu
Published
2005-04-05
Epub
2005-00-28
Pages
4966-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC555988
Subset
IM
Grants
NIGMS NIH HHS · R01 GM046638 · United States
NIGMS NIH HHS · R37 GM046638 · United States
NIGMS NIH HHS · GM 46638 · United States
External Links
PubMed source DOI: 10.1073/pnas.0409414102 PMC Full Text View journal details
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