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Genome Editing in Mammalian Cell Lines using CRISPR-Cas
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Enhancer reprogramming in mammalian genomes.

Mario A Flores1, Ivan Ovcharenko2

  • 1Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD, 20894, USA.

BMC Bioinformatics
|September 12, 2018
PubMed
Summary
This summary is machine-generated.

Evolutionary changes in regulatory elements, known as enhancer reprogramming, alter gene expression. This process, involving transcription factor binding site modifications, reshapes mammalian gene regulatory landscapes and can lead to new gene functions.

Keywords:
EnhancersEvolutionGene regulationTranscription factor binding sites

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Area of Science:

  • Genomics
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Changes in transcription factor binding sites (TFBS) within regulatory elements can alter their function.
  • These alterations, termed 'reprogramming,' modify the gene regulatory landscape during evolution.
  • Reprogramming events can be detrimental, neutral, or beneficial, influencing species fitness and population dynamics.

Purpose of the Study:

  • To identify and characterize reprogrammed enhancers (RPEs) by comparing human and mouse genomes.
  • To investigate the mechanisms driving enhancer reprogramming during mammalian evolution.
  • To assess the impact of enhancer reprogramming on gene expression and function.

Main Methods:

  • Comparative genomics analysis of tissue-specific enhancers in human and mouse genomes.
  • Profiling of evolutionary changes in TFBS content within enhancers.
  • Quantification of gene expression changes associated with RPEs.

Main Results:

  • Approximately 30% of mammalian enhancers have undergone reprogramming since human-mouse speciation.
  • Reprogramming of enhancers led to altered expression of flanking genes in 79% of cases.
  • Enhancer reprogramming primarily occurs through the acquisition of new TFBSs (72% of events).

Conclusions:

  • Enhancer reprogramming occurs within existing regulatory regions, contributing to the fine-tuning of gene regulation in mammals.
  • RPEs additively influence the mammalian gene regulatory program.
  • Enhancer reprogramming facilitates the acquisition of novel gene functions and expands regulatory landscapes.