A Genomic Regulatory Network for Development

Davidson, Eric H.; Rast, Jonathan P.; Oliveri, Paola; Ransick, Andrew; Calestani, Cristina; Yuh, Chiou-Hwa; Minokawa, Takuya; Amore, Gabriele; Hinman, Veronica F.; Arenas-Mena, César; Otim, Ochan; Brown, C. Titus; Livi, Carolina B.; Lee, Pei Yun; Revilla, Roger; Rust, Alistair G.; Pan, Zheng Jun; Schilstra, Maria J.; Clarke, Peter J.; Arnone, Maria Ina; Rowen, Lee; Cameron, R. Andrew; McClay, David R.; Hood, Leroy; Bolouri, Hamid

doi:10.1126/science.1069883

Cited by 1,392 publications

(977 citation statements)

References 44 publications

Supporting

Mentioning

951

Contrasting

Unclassified

Order By: Relevance

“…The evolution of development is to a large part based on changes in the cisregulatory elements of developmental genes [10]. Hence the evolutionary genetics of development requires tools for analyzing the rate and pattern of evolution of cis-regulatory sequences.…”

Section: Discussionmentioning

confidence: 99%

Surveying phylogenetic footprints in large gene clusters: applications to Hox cluster duplications

Prohaska

Fried

Flamm

et al. 2004

Molecular Phylogenetics and Evolution

View full text Add to dashboard Cite

Evolutionarily conserved non-coding genomic sequences represent a potentially rich source for the discovery of gene regulatory regions. Since these elements are subject to stabilizing selection they evolve much slower than adjacent non-functional DNA. These so-called phylogenetic footprints can be detected by comparison of the sequences surrounding orthologous genes in different species. In this paper we present a new method and an efficient software tool for the identification of corresponding footprints in long sequences from multiple species. This allows the evolutionary study of the origin and loss of phylogenetic footprints if sufficient number and appropriately placed species are included. We apply this method to the published sequences of HoxA clusters of shark, human, and the duplicated zebrafish and Takifugu clusters as well as the published HoxB cluster sequences. We find that there is a massive loss of sequence conservation in the intergenic region of the HoxA clusters, consistent with the finding in [Chiu et al., PNAS 99, 5492-5497 (2002)]. We further propose a simple model to estimate the loss of sequence conservation that can be attributed to gene loss and other structural reasons. We find that the loss of conservation after cluster duplication is more extensive than expected by this model. This suggests that binding site turnover and/or adaptive modification may also contribute to the loss of sequence conservation. We conclude that this method is suitable for the large scale study of the evolution of (putative) cis-regulatory elements.

show abstract

Section: Discussionmentioning

confidence: 99%

Surveying phylogenetic footprints in large gene clusters: applications to Hox cluster duplications

Prohaska

Fried

Flamm

et al. 2004

Molecular Phylogenetics and Evolution

View full text Add to dashboard Cite

show abstract

“…Complexes of nuclear proteins, called transcription factor complexes, bind to these cis-regulatory elements and enhance or repress transcription. Transcription only proceeds when the occupancy of dozens of these cis-regulatory elements is in an appropriate state [1,2]. Comprehensive identification and monitoring of these cisregulatory elements could lead to a better understanding of fundamental biological processes like development [3] and evolution [4].…”

Section: Introductionmentioning

confidence: 99%

Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

Mao¹,

Brody²

2007

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16 bp region of S. Cerevisiae chromosome 5 onto a gold surface. This 16 bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014 s −1 . We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase.

show abstract

“…2 ,… each represent a set of co-bound genes, each bound by the same transcription factor. Pipelines were developed for nine different TFBS detection methods and run over D and predictions compared to RegulonDB annotations to determine the core statistics.…”

Section: Resultsmentioning

confidence: 99%

The Motif Tool Assessment Platform (MTAP) for Sequence-Based Transcription Factor Binding Site Prediction Tools

Quest

Ali

2010

Methods in Molecular Biology

View full text Add to dashboard Cite

Predicting transcription factor binding sites (TFBS) from sequence is one of the most challenging problems in computational biology. The development of (semi-)automated computer-assisted prediction methods are needed to find TFBS over an entire genome, which is a first step in reconstructing mechanisms that controls gene activity. Bioinformatics journals continue to publish diverse methods for predicting TFBS on a monthly basis. To help practitioners in deciding which method to use to predict for a particular TFBS, we provide a platform to assess the quality and applicability of the available methods. Assessment tools allow researchers to determine how methods can be expected to perform on specific organisms or on specific transcription factor families. This chapter introduces the TFBS detection problem and reviews current strategies for evaluating algorithm effectiveness. In this chapter, a novel and robust assessment tool, the Motif Tool Assessment Platform (MTAP) is introduced and discussed.

show abstract

A Genomic Regulatory Network for Development

Cited by 1,392 publications

References 44 publications

Surveying phylogenetic footprints in large gene clusters: applications to Hox cluster duplications

Surveying phylogenetic footprints in large gene clusters: applications to Hox cluster duplications

Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

The Motif Tool Assessment Platform (MTAP) for Sequence-Based Transcription Factor Binding Site Prediction Tools

Contact Info

Product

Resources

About