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Enhancer turnover and conserved regulatory function in vertebrate evolution.

Sabina Domené1, Viviana F Bumaschny, Flávio S J de Souza

  • 1Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, , C1428ADN Buenos Aires, Argentina.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|November 13, 2013
PubMed
Summary
This summary is machine-generated.

Mammalian enhancers (nPE1, nPE2) for the proopiomelanocortin (Pomc) gene drive expression in zebrafish POMC neurons. This suggests conserved regulatory codes despite enhancer turnover during evolution.

Keywords:
comparative genomicshypothalamusmammalsproopiomelanocortinteleoststransgenic zebrafish

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Area of Science:

  • Evolutionary biology
  • Genetics
  • Neuroscience

Background:

  • Enhancers are crucial regulatory elements that evolve through sequence changes or turnover.
  • The proopiomelanocortin (Pomc) gene, encoding a prohormone, is vital for neuronal function in the hypothalamus and pituitary.
  • Mammalian hypothalamic Pomc expression is regulated by novel enhancers (nPE1, nPE2) derived from transposable elements.

Purpose of the Study:

  • To investigate the functional conservation of mammalian Pomc enhancers (nPE1, nPE2) in a non-mammalian vertebrate model.
  • To understand how gene regulatory landscapes evolve while maintaining ancestral expression patterns.
  • To identify and characterize the regulatory elements controlling Pomc expression in zebrafish.

Main Methods:

  • Generation of transgenic zebrafish expressing Pomc enhancers from mammals.
  • Analysis of gene expression patterns in transgenic zebrafish using reporter assays.
  • Comparative genomics to identify homologous regulatory regions in zebrafish.

Main Results:

  • Mammalian enhancers nPE1 and nPE2 successfully drive specific gene expression in hypothalamic POMC neurons of zebrafish.
  • These enhancers function independently of homologous counterparts in zebrafish, indicating de novo origin in mammals.
  • The zebrafish pomca neuronal regulatory region was identified and confirmed to be non-homologous to mammalian enhancers.

Conclusions:

  • Novel mammalian enhancers can functionally substitute for ancestral regulatory elements, preserving ancestral gene expression.
  • Enhancer turnover is a viable evolutionary mechanism for generating new regulatory functions that maintain essential gene expression.
  • The study provides insights into the evolution of gene regulation and the plasticity of cis- and trans-regulatory codes.