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CTCF: A misguided jack-of-all-trades in cancer cells

Julie Segueni1, Daan Noordermeer1

  • 1Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.

Computational and Structural Biotechnology Journal
|June 10, 2022
PubMed

Insights

Cancer progression involves altered gene transcription, where the three-dimensional (3D) genome organization, mediated by CTCF protein, is restructured. Perturbed CTCF function in cancer can activate oncogenes via enhancer hijacking.

Area of Science:

  • Genomics
  • Cancer Biology
  • Epigenetics

Background:

  • Cancer development is linked to disrupted transcriptional programs.
  • The three-dimensional (3D) genome organization is a key regulator of gene transcription.
  • CTCF protein is crucial for 3D genome architecture in normal cells.

Purpose of the Study:

  • To summarize CTCF's role in human genome's 3D organization.
  • To discuss how altered CTCF function in cancer leads to oncogene activation.
  • To highlight non-canonical CTCF functions in cancer emergence.

Main Methods:

  • Review of existing literature on CTCF and 3D genome organization.
  • Analysis of mechanisms of oncogene activation through enhancer hijacking.
  • Discussion of computational approaches for identifying CTCF binding and 3D genome alterations.

Main Results:

  • CTCF is central to the multi-level organization of the 3D genome.
  • Dysregulated CTCF binding and function in cancer can activate oncogenes, primarily via enhancer hijacking.
  • Non-canonical roles of CTCF contribute to cancer development.

Conclusions:

  • CTCF plays a critical role in maintaining genome architecture and preventing oncogene activation.
  • Understanding CTCF's function in 3D genome organization is vital for cancer research.
  • Computational tools can aid in identifying genomic alterations related to CTCF in cancer.
Keywords:
3C, chromosome conformation capture3D genome organizationAS, alternative splicingCBS, CTCF binding siteCNV, copy number variationCRE, cis-regulatory elementCT, chromosome territoryCTCFCancer genomesComputational biologyDSB, DNA double strand breakEnhancer hijackingFISH, fluorescence in situ hybridizationGIST, gastrointestinal stromal tumorsHi-C, high-throughput 3CRBR, RNA binding regionSE, super enhancerT-ALL, T cell acute lymphoblastic leukemiaTAD, topologically associating domainTADsTopologically associating domainsTumor suppressorZF, zinc finger

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