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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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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...
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Author Correction: CpG island turnover events predict evolutionary changes in enhancer activity.

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Updated: Jun 24, 2025

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CpG island turnover events predict evolutionary changes in enhancer activity.

Acadia A Kocher1,2, Emily V Dutrow1,3, Severin Uebbing1,4

  • 1Department of Genetics, Yale School of Medicine, New Haven, CT, 06510, USA.

Genome Biology
|June 13, 2024
PubMed
Summary
This summary is machine-generated.

CpG island (CGI) turnover drives gene regulatory evolution and biological diversity in mammals. Species-specific CGIs are linked to unique enhancer activity and gene expression, contributing to trait evolution.

Keywords:
Comparative genomicsGene regulationOrphan CpG islandsTranscriptional enhancer evolution

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Molecular biology

Background:

  • Genetic changes in transcriptional enhancers influence species diversity.
  • Nucleotide substitutions, transposition, and indels alter enhancer function.
  • CpG islands (CGIs) impact enhancer activity, prompting investigation into their evolutionary role.

Purpose of the Study:

  • To investigate how CpG island (CGI) turnover across species contributes to enhancer evolution.
  • To determine the association between CGI content and enhancer activity.
  • To explore the role of CGI turnover in gene regulatory innovation and trait evolution.

Main Methods:

  • Integration of CGI maps and enhancer activity histone modifications across nine mammalian species.
  • Analysis of CGI turnover and species-specific CGI enrichment in enhancers.
  • Gene expression analysis for genes linked to enhancers with species-specific CGIs.
  • Utilizing a humanized mouse model to study a specific Human Gain Enhancer (HGE).

Main Results:

  • CGI content in enhancers correlates with increased histone modification levels.
  • Widespread CGI turnover observed across species, with species-specific CGIs linked to species-specific enhancer activity.
  • Genes associated with species-specific CGIs show concordant expression biases, indicating regulatory innovation.
  • CGI turnover implicated in the evolution of Human Gain Enhancers (HGEs), potentially contributing to human-specific traits.

Conclusions:

  • CpG island (CGI) turnover is a key mechanism for gene regulatory changes in mammalian evolution.
  • This process contributes to the evolution of biological diversity and species-specific traits.
  • CGI turnover plays a role in the development of unique mammalian characteristics, including human-specific traits.