Cited by 1,246Genomics and Chromatin DynamicsChromosomal and Genetic VariationsDevelopmental Biology and Gene Regulation

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Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence

Wittkopp, Patricia J., Kalay, Gizem·2012·Nature Reviews Genetics

DOI 10.1038/nrg3095

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Abstract

Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

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Authors: Wittkopp, P. J., & Kalay, G.
Affiliations: University of Michigan (US)
Corresponding author: Wittkopp, Patricia J.
ORCID: Wittkopp, Patricia J.
Kalay, Gizem
Venue: Nature Reviews Genetics
Publisher: Springer Science and Business Media LLC
Published: 2011-12-06
Volume: 13
Issue: 1
Pages: 59-69
ISSN: 1471-0056 (ISSN-L)
1471-0064
DOI: 10.1038/nrg3095
OpenAlex: W2089806726
Cited by: 1,231
References: 103
Citations by year: 2026: 112 · 2025: 128 · 2024: 129 · 2023: 112 · 2022: 103 · 2021: 99 · 2020: 95 · 2019: 74 · 2018: 74 · 2017: 55 · 2016: 75 · 2015: 66 · 2014: 48 · 2013: 41 · 2012: 18
FWCI: 3.11
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: cis-regulatory elements, enhancers, promoter, cis-regulatory divergence, phenotypic evolution, transcription factor binding, genetic mutations, gene expression regulation, phenotypic diversity
MeSH terms: Animals, Base Sequence, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Regulatory Sequences, Nucleic Acid, Genome, Conserved Sequence, Evolution, Molecular, Computational Biology, Genomics, Mice

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Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence

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