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ZNF146/OZF and ZNF507 target LINE-1 sequences.

Kevin M Creamer1, Eric C Larsen1, Jeanne B Lawrence1

  • 1Department of Neurology and Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA.

G3 (Bethesda, Md.)
|January 31, 2022
PubMed
Summary

Two C2H2 zinc finger proteins, ZNF146 and ZNF507, bind to distinct sites within LINE-1 elements in the human genome. ZNF507 interacts with PRMT5, suggesting a role in regulating gene expression via methylation.

Keywords:
L1LINE-1OZFPRMT5ZNF146ZNF507transposable element

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • Repetitive sequences, including transposable elements (TEs), constitute nearly half of the human genome.
  • While active TEs require repression for genomic stability, fragmented TEs can regulate gene expression and genome organization.
  • Understanding the proteins interacting with TEs is crucial for deciphering their regulatory roles.

Purpose of the Study:

  • To identify proteins broadly enriched on human transposable elements using ChIP-seq data.
  • To investigate the binding specificities and functions of ZNF146 and ZNF507 on LINE-1 elements.
  • To explore the functional consequences of ZNF146 and ZNF507 disruption and their potential interactions.

Main Methods:

  • Analysis of published ChIP-seq datasets to identify protein enrichment on TEs.
  • CRISPR/Cas9-mediated gene disruption of ZNF146 and ZNF507 in HEK293 cells.
  • RNA sequencing to assess gene expression changes post-disruption.
  • Co-immunoprecipitation to identify protein-protein interactions.

Main Results:

  • ZNF146 and ZNF507 were identified as proteins enriched on transposable elements, specifically binding to LINE-1 ORF2.
  • ZNF146 binds to both old and young LINE-1 elements, whereas ZNF507 preferentially binds to young LINE-1 sequences.
  • Disruption of ZNF507 led to modest changes in gene expression, and ZNF507 was found to physically interact with PRMT5.

Conclusions:

  • ZNF146 and ZNF507 are novel proteins that bind to specific regions of LINE-1 elements.
  • ZNF507's preferential binding to young LINE-1 elements and interaction with PRMT5 suggest a role in regulating LINE-1 activity and host gene expression.
  • These findings contribute to understanding the regulatory roles of repetitive elements in the human genome.