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Cis-regulatory Sequences

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

Cis-regulatory Sequences

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

Genetic Screens

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...

Polygenic Traits

Polygenic Traits

When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...

Polygenic Traits

Polygenic Traits

When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...

Cooperative Binding of Transcription Regulators

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...

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Related Experiment Video

Updated: Jun 2, 2026

Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes

Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes

Published on: May 31, 2011

Systematic detection of polygenic cis-regulatory evolution.

Hunter B Fraser¹, Tomas Babak, John Tsang

¹Rosetta Inpharmatics, Seattle, Washington, United States of America.

|April 13, 2011

Summary

Natural selection frequently drives morphological changes through cis-regulatory gene expression. This study reveals widespread, polygenic cis-regulatory adaptations in mouse subspecies, impacting diverse traits like growth and memory.

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Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes

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Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA)

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High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture (4C-seq)

High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture (4C-seq)

Published on: October 5, 2018

Area of Science:

Evolutionary biology
Genomics
Developmental biology

Background:

The role of cis-regulation in morphological adaptation is increasingly recognized but empirically limited.
Previous studies focused on single genes, leaving network-level cis-regulatory evolution poorly understood.

Purpose of the Study:

To perform a genome-wide test for natural selection acting on cis-regulation in mouse subspecies.
To investigate how selection on cis-regulation operates across gene pathways and networks.

Main Methods:

Applied a genome-wide test for selection on cis-regulation to two subspecies of Mus musculus.
Utilized quantitative trait loci and a causality-testing framework to identify candidate genes.
Confirmed predicted phenotypic differences experimentally.

Main Results:

Identified lineage-specific selection at over 100 genes involved in growth, locomotion, and memory.
Demonstrated that cis-regulatory adaptation is widespread and can be highly polygenic.
Confirmed predicted phenotypic differences in four tested cases.

Conclusions:

Cis-regulatory changes at numerous functionally related genes drive coordinated adaptations.
These polygenic adaptations contribute to divergence in morphological, physiological, and behavioral phenotypes.
Gene expression evolution is a significant mechanism shaping species diversity.