When needles look like hay: How to find tissue-specific enhancers in model organism genomes

A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is available to distinguish them from any other type of genomic non-coding sequence. Therefore, researchers often have to identify these element...

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Bibliographic Details
Published inDevelopmental biology Vol. 350; no. 2; pp. 239 - 254
Main Authors Haeussler, Maximilian, Joly, Jean-Stéphane
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.02.2011
Elsevier
Subjects
Algorithms
Animals
Animals, Genetically Modified
Base Sequence
binding sites
Cis-regulation
Cis-regulatory element
Computer applications
Data processing
Enhancer Elements, Genetic
Enhancers
Fish
genes
Genes, Regulator
Genome
Genome analysis
Genomes
genomics
guidelines
Hay
High-Throughput Screening Assays
Humans
Life Sciences
Medaka
Neurons and Cognition
Non-coding elements
Nucleotides
Organ Specificity
Promoters
researchers
Reviews
Transcriptional regulation
Transgenesis
Transgenic animals
Zebrafish
Non-coding elements
Enhancers
Cis-regulation
Genome analysis
Medaka
Fish
Zebrafish
Transcriptional regulation
Transgenesis
Cis-regulatory element
Online AccessGet full text
ISSN0012-1606
1095-564X
1095-564X
DOI10.1016/j.ydbio.2010.11.026

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Abstract A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is available to distinguish them from any other type of genomic non-coding sequence. Therefore, researchers often have to identify these elements by elaborate in vivo screens, testing individual regions until the right one is found. Here, based on many examples from the literature, we summarize how functional enhancers have been isolated from other elements in the genome and how they have been characterized in transgenic animals. Covering computational and experimental studies, we provide an overview of the global properties of cis-regulatory elements, like their specific interactions with promoters and target gene distances. We describe conserved non-coding elements (CNEs) and their internal structure, nucleotide composition, binding site clustering and overlap, with a special focus on developmental enhancers. Conflicting data and unresolved questions on the nature of these elements are highlighted. Our comprehensive overview of the experimental shortcuts that have been found in the different model organism communities and the new field of high-throughput assays should help during the preparation phase of a screen for enhancers. The review is accompanied by a list of general guidelines for such a project. ► For in vivo tests of cis-regulatory region, various experimental shortcuts have been found. ► Cross-species conservation reduces the search space. ► Long-range effects and promoter interactions can complicate the identification. ► Cell culture essays might be of limited use for developmental enhancers. ► Sequence predictions enrich but are not generic enough for most developing tissues.
AbstractList A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is available to distinguish them from any other type of genomic non-coding sequence. Therefore, researchers often have to identify these elements by elaborate in vivo screens, testing individual regions until the right one is found. Here, based on many examples from the literature, we summarize how functional enhancers have been isolated from other elements in the genome and how they have been characterized in transgenic animals. Covering computational and experimental studies, we provide an overview of the global properties of cis-regulatory elements, like their specific interactions with promoters and target gene distances. We describe conserved non-coding elements (CNEs) and their internal structure, nucleotide composition, binding site clustering and overlap, with a special focus on developmental enhancers. Conflicting data and unresolved questions on the nature of these elements are highlighted. Our comprehensive overview of the experimental shortcuts that have been found in the different model organism communities and the new field of high-throughput assays should help during the preparation phase of a screen for enhancers. The review is accompanied by a list of general guidelines for such a project.
A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is available to distinguish them from any other type of genomic non-coding sequence. Therefore, researchers often have to identify these elements by elaborate in vivo screens, testing individual regions until the right one is found. Here, based on many examples from the literature, we summarize how functional enhancers have been isolated from other elements in the genome and how they have been characterized in transgenic animals. Covering computational and experimental studies, we provide an overview of the global properties of cis-regulatory elements, like their specific interactions with promoters and target gene distances. We describe conserved non-coding elements (CNEs) and their internal structure, nucleotide composition, binding site clustering and overlap, with a special focus on developmental enhancers. Conflicting data and unresolved questions on the nature of these elements are highlighted. Our comprehensive overview of the experimental shortcuts that have been found in the different model organism communities and the new field of high-throughput assays should help during the preparation phase of a screen for enhancers. The review is accompanied by a list of general guidelines for such a project.A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is available to distinguish them from any other type of genomic non-coding sequence. Therefore, researchers often have to identify these elements by elaborate in vivo screens, testing individual regions until the right one is found. Here, based on many examples from the literature, we summarize how functional enhancers have been isolated from other elements in the genome and how they have been characterized in transgenic animals. Covering computational and experimental studies, we provide an overview of the global properties of cis-regulatory elements, like their specific interactions with promoters and target gene distances. We describe conserved non-coding elements (CNEs) and their internal structure, nucleotide composition, binding site clustering and overlap, with a special focus on developmental enhancers. Conflicting data and unresolved questions on the nature of these elements are highlighted. Our comprehensive overview of the experimental shortcuts that have been found in the different model organism communities and the new field of high-throughput assays should help during the preparation phase of a screen for enhancers. The review is accompanied by a list of general guidelines for such a project.
A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is available to distinguish them from any other type of genomic non-coding sequence. Therefore, researchers often have to identify these elements by elaborate in vivo screens, testing individual regions until the right one is found. Here, based on many examples from the literature, we summarize how functional enhancers have been isolated from other elements in the genome and how they have been characterized in transgenic animals. Covering computational and experimental studies, we provide an overview of the global properties of cis-regulatory elements, like their specific interactions with promoters and target gene distances. We describe conserved non-coding elements (CNEs) and their internal structure, nucleotide composition, binding site clustering and overlap, with a special focus on developmental enhancers. Conflicting data and unresolved questions on the nature of these elements are highlighted. Our comprehensive overview of the experimental shortcuts that have been found in the different model organism communities and the new field of high-throughput assays should help during the preparation phase of a screen for enhancers. The review is accompanied by a list of general guidelines for such a project. ► For in vivo tests of cis-regulatory region, various experimental shortcuts have been found. ► Cross-species conservation reduces the search space. ► Long-range effects and promoter interactions can complicate the identification. ► Cell culture essays might be of limited use for developmental enhancers. ► Sequence predictions enrich but are not generic enough for most developing tissues.
Author Haeussler, Maximilian
Joly, Jean-Stéphane
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Wed Oct 01 14:08:11 EDT 2025
Thu Oct 02 05:29:48 EDT 2025
Sat Sep 27 17:17:59 EDT 2025
Mon Jul 21 06:02:46 EDT 2025
Wed Oct 01 01:25:13 EDT 2025
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Wed Dec 27 19:05:03 EST 2023
Tue May 20 10:00:13 EDT 2025
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Issue 2
Keywords Non-coding elements
Enhancers
Cis-regulation
Genome analysis
Medaka
Fish
Zebrafish
Transcriptional regulation
Transgenesis
Cis-regulatory element
Language English
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PublicationTitle Developmental biology
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Snippet A major prerequisite for the investigation of tissue-specific processes is the identification of cis-regulatory elements. No generally applicable technique is...
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SubjectTerms Algorithms
Animals
Animals, Genetically Modified
Base Sequence
binding sites
Cis-regulation
Cis-regulatory element
Computer applications
Data processing
Enhancer Elements, Genetic
Enhancers
Fish
genes
Genes, Regulator
Genome
Genome analysis
Genomes
genomics
guidelines
Hay
High-Throughput Screening Assays
Humans
Life Sciences
Medaka
Neurons and Cognition
Non-coding elements
Nucleotides
Organ Specificity
Promoters
researchers
Reviews
Transcriptional regulation
Transgenesis
Transgenic animals
Zebrafish
Title When needles look like hay: How to find tissue-specific enhancers in model organism genomes
URI https://dx.doi.org/10.1016/j.ydbio.2010.11.026
https://www.ncbi.nlm.nih.gov/pubmed/21130761
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https://www.proquest.com/docview/883012962
https://hal.science/hal-00586182
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