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CTCF binding landscape in jawless fish with reference to Hox cluster evolution.

Mitsutaka Kadota1, Yuichiro Hara1, Kaori Tanaka1

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The CCCTC-binding factor (CTCF) protein

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Area of Science:

  • Genomics
  • Epigenetics
  • Evolutionary Biology

Background:

  • The CCCTC-binding factor (CTCF) is crucial for chromatin organization and acts as an insulator in animal genomes.
  • Knowledge of CTCF binding properties is primarily limited to mammals.
  • Understanding CTCF's evolutionary conservation provides insights into fundamental genomic regulation.

Purpose of the Study:

  • To identify and characterize CTCF homologs in jawless fishes.
  • To investigate CTCF binding sites and motifs in the Arctic lamprey using ChIP-seq.
  • To explore the evolutionary history of CTCF-based epigenomic regulation.

Main Methods:

  • Phylogenetic analysis of CTCF homologs.
  • Chromatin immunoprecipitation followed by sequencing (ChIP-seq) in the Arctic lamprey.
  • Comparative analysis of CTCF binding sites and motifs across vertebrates.

Main Results:

  • Identified a unique lamprey paralog, CTCF2, arising from gene duplication.
  • CTCF binding sites in lamprey are comparable in number to those in chicken and human.
  • Lamprey CTCF utilizes a conserved two-part binding motif, suggesting ancient origins.
  • Discovered a lamprey-specific reinforcement of CTCF binding within Hox clusters (Hox1-4).

Conclusions:

  • CTCF-based chromatin organization mechanisms are ancient, dating back to the last common vertebrate ancestor.
  • The study reveals conserved and unique aspects of CTCF binding and function across vertebrates.
  • Provides a foundation for broader comparative epigenomic studies in vertebrates.