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An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3.

Yuri S Odaka1, Takahide Tohmonda1, Atsushi Toyoda2

  • 1Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako-shi, Saitama, 351-0198, Japan.

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|October 10, 2018
PubMed
Summary
This summary is machine-generated.

Researchers identified a key regulatory element, Zic3-ME, essential for Zic3 gene expression in mesodermal tissues. This element is crucial for vertebrate development and integrates into gene regulatory networks.

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Zic3 is a zinc finger protein vital for meso-ectodermal tissue development in vertebrates.
  • It plays critical roles in neural tube formation, axial skeleton development, left-right body axis determination, and embryonic stem cell pluripotency.

Purpose of the Study:

  • To characterize the cis-regulatory elements controlling Zic3 gene expression.
  • To identify enhancers responsible for Zic3 expression in meso-ectodermal tissues.

Main Methods:

  • Screening of human-chicken conserved noncoding sequences for enhancer activity using chick whole-embryo electroporation.
  • Assessing reporter gene expression in chicken and mouse embryos.
  • Analyzing DNase hypersensitive regions and transcription factor binding in ES cells, mesoderm, and neural progenitors.

Main Results:

  • A novel mesodermal enhancer (Zic3-ME) located in the 3' flanking region was identified.
  • Zic3-ME demonstrated robust reporter gene expression in mesodermal tissues of both chicken and mouse embryos.
  • This enhancer was essential for endogenous Zic3 expression in mouse mesoderm and its core region is bound by key developmental transcription factors (T, Eomes, Lef1, Nanog, Oct4, Zic2).

Conclusions:

  • Zic3-ME is an essential cis-regulatory element for proper Zic3 expression in vertebrates.
  • It functions as a regulatory hub within a gene network involving Zic3 and other developmental factors.
  • The ancestral origin of Zic3-ME from a mitochondrial enzyme sequence suggests evolutionary integration into developmental gene regulation.