Functional Domains of ZFP809 Essential for Nuclear Localization and Gene Silencing

Yu Ichida1, Yuko Utsunomiya1, Toru Yasuda1

  • 1Department of Human Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.

Plos One
|September 30, 2015
PubMed

Insights

Zinc finger protein 809 (ZFP809) silences transduced genes by binding retroviral vectors. The KRAB A box is essential for this gene silencing, with zinc fingers playing accessory roles.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Zinc finger protein 809 (ZFP809), a KRAB-ZFP family member, is highly expressed in mouse immature cells.
  • ZFP809 inhibits transduced gene expression from MoMLV-type retroviral vectors via epigenetic silencing.
  • The specific domains of ZFP809 responsible for gene silencing were previously undetermined.

Purpose of the Study:

  • To identify the critical domains of ZFP809 responsible for gene silencing.
  • To investigate the roles of ZFP809's KRAB domain and zinc fingers in gene silencing.
  • To understand the interaction between ZFP809, KAP1, and retroviral vectors.

Main Methods:

  • Generated and analyzed truncated and mutated ZFP809 proteins.
  • Assessed subcellular localization, gene silencing ability, and PBS binding affinity.
  • Investigated the interaction between ZFP809 and KAP1.

Main Results:

  • The KRAB A box of ZFP809 is essential for gene silencing, subcellular localization, and PBS binding.
  • Specific zinc fingers contribute accessory roles in ZFP809-mediated gene silencing.
  • Interaction between KAP1 and the ZFP809 KRAB A box is crucial for KAP1-dependent gene silencing.

Conclusions:

  • The KRAB A box is the primary functional domain for ZFP809-mediated gene silencing.
  • Zinc fingers modulate ZFP809's gene silencing activity.
  • KAP1 interaction with the KRAB A box is vital for ZFP809's epigenetic control of target genes.

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